Difference between revisions of "HAEM5:Hairy cell leukaemia"

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{{DISPLAYTITLE:Hairy cell leukaemia}}
 
{{DISPLAYTITLE:Hairy cell leukaemia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+
 
 +
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
  
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Hairy Cell Leukemia]].
+
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Hairy Cell Leukemia]].
 
}}</blockquote>
 
}}</blockquote>
 +
 +
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
 +
 
==Primary Author(s)*==
 
==Primary Author(s)*==
  
*Snehal Patel, MD, PhD  
+
*Michael Lack, DO, Shivani Golem, PhD FACMG
 
__TOC__
 
__TOC__
  
==Cancer Category / Type==
+
==WHO Classification of Disease==
  
*[[HAEM4:Mature B-Cell Neoplasms|Mature B-Cell Neoplasm]]
+
{| class="wikitable"
 
+
!Structure
==Cancer Sub-Classification / Subtype==
+
!Disease
 
+
|-
*Hairy Cell Leukemia
+
|Book
 +
|Haematolymphoid Tumours (5th ed.)
 +
|-
 +
|Category
 +
|B-cell lymphoid proliferations and lymphomas
 +
|-
 +
|Family
 +
|Mature B-cell neoplasms
 +
|-
 +
|Type
 +
|Splenic B-cell lymphomas and leukaemias
 +
|-
 +
|Subtype(s)
 +
|Hairy cell leukaemia
 +
|}
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
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*Incidence (age adjusted) ~ 0.3/100,000
 
*Incidence (age adjusted) ~ 0.3/100,000
 
*2% of lymphoid leukemias
 
*2% of lymphoid leukemias
*Median age:  ~60 years
+
*Median age:  58 years, rarely in patients in their 20s
*Males:Females:  4:1 to 5:1
+
*Males:Females:  4:1
 
*Whites >> Blacks
 
*Whites >> Blacks
 
*78% to 92% 5yr survival
 
*78% to 92% 5yr survival
Line 43: Line 61:
  
  
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref>{{Cite journal|last=Lr|first=Teras|last2=Ce|first2=DeSantis|last3=Jr|first3=Cerhan|last4=Lm|first4=Morton|last5=A|first5=Jemal|last6=Cr|first6=Flowers|date=2016|title=2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/27618563/|language=en|pmid=27618563}}</ref></blockquote>
+
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref>{{Cite journal|last=Lr|first=Teras|last2=Ce|first2=DeSantis|last3=Jr|first3=Cerhan|last4=Lm|first4=Morton|last5=A|first5=Jemal|last6=Cr|first6=Flowers|date=2016|title=2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/27618563/|language=en|pmid=27618563}}</ref></blockquote>
 
==Clinical Features==
 
==Clinical Features==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|
 
+
*Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
+
*B-symptoms (weight loss, fever, night sweats)
 
+
*Fatigue
EXAMPLE Fatigue
+
*Splenic enlargement and discomfort
 
+
*Recurrent infections
EXAMPLE Lymphadenopathy (uncommon)
+
*Lymphadenopathy (rare)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
+
|Pancytopenia (monocytopenia is characteristic)
 
+
Lymphocytosis (low level)
EXAMPLE Lymphocytosis (low level)
 
 
|}
 
|}
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
  
  
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*B-symptoms (weight loss, fever, night sweats)
 
*B-symptoms (weight loss, fever, night sweats)
 
*Fatigue
 
*Fatigue
*Splenic enlargement and discomfort
+
*LUQ pain (splenomegaly)
*Recurrent infections
 
 
*Lymphadenopathy (uncommon)
 
*Lymphadenopathy (uncommon)
  
Line 81: Line 95:
 
*Monocytopenia
 
*Monocytopenia
 
*Lymphocytosis (low level)
 
*Lymphocytosis (low level)
 
+
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2">{{Cite journal|last=Grever|first=Michael R.|last2=Abdel-Wahab|first2=Omar|last3=Andritsos|first3=Leslie A.|last4=Banerji|first4=Versha|last5=Barrientos|first5=Jacqueline|last6=Blachly|first6=James S.|last7=Call|first7=Timothy G.|last8=Catovsky|first8=Daniel|last9=Dearden|first9=Claire|date=2017|title=Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia|url=https://ashpublications.org/blood/article/129/5/553/36153/Consensus-guidelines-for-the-diagnosis-and|journal=Blood|language=en|volume=129|issue=5|pages=553–560|doi=10.1182/blood-2016-01-689422|issn=0006-4971|pmc=PMC5290982|pmid=27903528}}</ref></blockquote>
 
 
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2">{{Cite journal|last=Grever|first=Michael R.|last2=Abdel-Wahab|first2=Omar|last3=Andritsos|first3=Leslie A.|last4=Banerji|first4=Versha|last5=Barrientos|first5=Jacqueline|last6=Blachly|first6=James S.|last7=Call|first7=Timothy G.|last8=Catovsky|first8=Daniel|last9=Dearden|first9=Claire|date=2017|title=Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia|url=https://ashpublications.org/blood/article/129/5/553/36153/Consensus-guidelines-for-the-diagnosis-and|journal=Blood|language=en|volume=129|issue=5|pages=553–560|doi=10.1182/blood-2016-01-689422|issn=0006-4971|pmc=PMC5290982|pmid=27903528}}</ref></blockquote>
 
 
</blockquote>
 
</blockquote>
 
==Sites of Involvement==
 
==Sites of Involvement==
 
  
 
*Spleen (red pulp)
 
*Spleen (red pulp)
 
*Bone marrow
 
*Bone marrow
*liver
+
*Liver
*Blood
+
*Blood (small number)
 
+
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
 
 
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
 
 
==Morphologic Features==
 
==Morphologic Features==
  
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<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
+
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
 
==Immunophenotype==
 
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||EXAMPLE CD1
+
|Positive (B-cell lineage markersl)||CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
 
|-
 
|-
|Positive (subset)||EXAMPLE CD2
+
|Positive||CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
 
|-
 
|-
|Negative (universal)||EXAMPLE CD3
+
|Negative||CD5, CD10 (10-20% may be positive), CD23, CD27
|-
 
|Negative (subset)||EXAMPLE CD4
 
 
|}
 
|}
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
  
  
Line 142: Line 147:
  
  
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
+
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
 
</blockquote>
 
</blockquote>
 
==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
  
Put your text here and fill in the table
+
*No consistent gene fusions
 
+
*Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL<ref name=":3" />
{| class="wikitable sortable"
+
*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4" />
|-
+
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
 
!Diagnostic Significance (Yes, No or Unknown)
 
!Prognostic Significance (Yes, No or Unknown)
 
!Therapeutic Significance (Yes, No or Unknown)
 
!Notes
 
|-
 
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
 
EXAMPLE 30% (add reference)
 
|Yes
 
|No
 
|Yes
 
|EXAMPLE
 
 
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
 
|}
 
 
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
 
  
 
*No consistent gene fusions
 
*No consistent gene fusions
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Individual Region Genomic Gain/Loss/LOH
 
* Individual Region Genomic Gain/Loss/LOH
Line 211: Line 198:
 
==Individual Region Genomic Gain / Loss / LOH==
 
==Individual Region Genomic Gain / Loss / LOH==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
+
{| class="wikitable"
 
+
!chromosome<ref name=":5" /><ref name=":6" />
{| class="wikitable sortable"
+
!Alteration
 +
!Consequence
 +
!Prevalence
 +
|-
 +
|14q22-32
 +
|Heterozygous deletion
 +
|Uncertain
 +
|33%
 
|-
 
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+
|7q
!Diagnostic Significance (Yes, No or Unknown)
+
|Heterozygous deletion
!Prognostic Significance (Yes, No or Unknown)
+
|LOH of BRAF p.Val600Glu
!Therapeutic Significance (Yes, No or Unknown)
+
|9-21%
!Notes
 
 
|-
 
|-
|EXAMPLE
+
|13q
 
+
|Deletion
7
+
|Loss of RB1, miR-15a, and miR-16-1
|EXAMPLE Loss
+
|6%
|EXAMPLE
 
 
 
chr7:1- 159,335,973 [hg38]
 
|EXAMPLE
 
 
 
chr7
 
|Yes
 
|Yes
 
|No
 
|EXAMPLE
 
 
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
 
|-
 
|-
|EXAMPLE
+
|5
 +
|Gain
 +
|Uncertain
 +
|9-15%
 +
|}
  
8
+
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
|EXAMPLE Gain
 
|EXAMPLE
 
 
 
chr8:1-145,138,636 [hg38]
 
|EXAMPLE
 
 
 
chr8
 
|No
 
|No
 
|No
 
|EXAMPLE
 
 
 
Common recurrent secondary finding for t(8;21) (add reference).
 
|}
 
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
 
  
 
*Recurrent gains and losses were found to be absent in HCLs from Chinese patients<ref>{{Cite journal|last=Zhang|first=Rui|last2=Wu|first2=Yongli|last3=Wang|first3=Xianfu|last4=Lu|first4=Xianglan|last5=Li|first5=Yan|last6=Li|first6=Shibo|last7=Yan|first7=Xiaojing|date=2020|title=Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese|url=https://www.ncbi.nlm.nih.gov/pubmed/32132867|journal=International Journal of Medical Sciences|volume=17|issue=3|pages=325–331|doi=10.7150/ijms.39307|issn=1449-1907|pmc=7053350|pmid=32132867}}</ref>
 
*Recurrent gains and losses were found to be absent in HCLs from Chinese patients<ref>{{Cite journal|last=Zhang|first=Rui|last2=Wu|first2=Yongli|last3=Wang|first3=Xianfu|last4=Lu|first4=Xianglan|last5=Li|first5=Yan|last6=Li|first6=Shibo|last7=Yan|first7=Xiaojing|date=2020|title=Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese|url=https://www.ncbi.nlm.nih.gov/pubmed/32132867|journal=International Journal of Medical Sciences|volume=17|issue=3|pages=325–331|doi=10.7150/ijms.39307|issn=1449-1907|pmc=7053350|pmid=32132867}}</ref>
  
 
{| class="wikitable"
 
{| class="wikitable"
!chromosome<ref>{{Cite journal|last=Durham|first=Benjamin H.|last2=Getta|first2=Bartlomiej|last3=Dietrich|first3=Sascha|last4=Taylor|first4=Justin|last5=Won|first5=Helen|last6=Bogenberger|first6=James M.|last7=Scott|first7=Sasinya|last8=Kim|first8=Eunhee|last9=Chung|first9=Young Rock|date=2017|title=Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations|url=https://www.ncbi.nlm.nih.gov/pubmed/28801450|journal=Blood|volume=130|issue=14|pages=1644–1648|doi=10.1182/blood-2017-01-765107|issn=1528-0020|pmc=5630011|pmid=28801450}}</ref><ref>{{Cite journal|last=A|first=Nordgren|last2=M|first2=Corcoran|last3=A|first3=Sääf|last4=A|first4=Bremer|last5=Hc|first5=Kluin-Nelemans|last6=J|first6=Schoumans|last7=D|first7=Grandér|date=2010|title=Characterisation of Hairy Cell Leukaemia by Tiling Resolution Array-Based Comparative Genome Hybridisation: A Series of 13 Cases and Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/19682064/|language=en|pmid=19682064}}</ref>
+
!chromosome<ref name=":5">{{Cite journal|last=Durham|first=Benjamin H.|last2=Getta|first2=Bartlomiej|last3=Dietrich|first3=Sascha|last4=Taylor|first4=Justin|last5=Won|first5=Helen|last6=Bogenberger|first6=James M.|last7=Scott|first7=Sasinya|last8=Kim|first8=Eunhee|last9=Chung|first9=Young Rock|date=2017|title=Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations|url=https://www.ncbi.nlm.nih.gov/pubmed/28801450|journal=Blood|volume=130|issue=14|pages=1644–1648|doi=10.1182/blood-2017-01-765107|issn=1528-0020|pmc=5630011|pmid=28801450}}</ref><ref name=":6">{{Cite journal|last=A|first=Nordgren|last2=M|first2=Corcoran|last3=A|first3=Sääf|last4=A|first4=Bremer|last5=Hc|first5=Kluin-Nelemans|last6=J|first6=Schoumans|last7=D|first7=Grandér|date=2010|title=Characterisation of Hairy Cell Leukaemia by Tiling Resolution Array-Based Comparative Genome Hybridisation: A Series of 13 Cases and Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/19682064/|language=en|pmid=19682064}}</ref>
 
!Alteration
 
!Alteration
 
!Consequence
 
!Consequence
Line 290: Line 259:
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
  
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
+
IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7" />.
  
{| class="wikitable sortable"
+
<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
|-
 
!Chromosomal Pattern
 
!Diagnostic Significance (Yes, No or Unknown)
 
!Prognostic Significance (Yes, No or Unknown)
 
!Therapeutic Significance (Yes, No or Unknown)
 
!Notes
 
|-
 
|EXAMPLE
 
  
Co-deletion of 1p and 18q
+
*IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7">{{Cite journal|last=Arons|first=Evgeny|last2=Kreitman|first2=Robert J.|date=2011|title=Molecular variant of hairy cell leukemia with poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21599610|journal=Leukemia & Lymphoma|volume=52 Suppl 2|pages=99–102|doi=10.3109/10428194.2011.565841|issn=1029-2403|pmid=21599610}}</ref>.
|Yes
 
|No
 
|No
 
|EXAMPLE:
 
 
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
|}
 
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
 
 
 
*IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref>{{Cite journal|last=Arons|first=Evgeny|last2=Kreitman|first2=Robert J.|date=2011|title=Molecular variant of hairy cell leukemia with poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21599610|journal=Leukemia & Lymphoma|volume=52 Suppl 2|pages=99–102|doi=10.3109/10428194.2011.565841|issn=1029-2403|pmid=21599610}}</ref>.
 
  
 
</blockquote>
 
</blockquote>
 
==Gene Mutations (SNV / INDEL)==
 
==Gene Mutations (SNV / INDEL)==
 
+
{| class="wikitable"
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
+
|-
 
+
!Gene<sup>‡</sup>!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism
{| class="wikitable sortable"
+
(LOF/GOF/Other)
 +
!Prevalence<ref name=":1" />
 +
|-
 +
|[[BRAF]]||Oncogene||GOF||70-100%*
 +
|-
 +
|[[MAP2K1]]
 +
|Oncogene
 +
|GOF
 +
|0-22%*
 +
|-
 +
|[[TP53]]
 +
|Tumor Suppressor
 +
|LOF
 +
|2-28%
 +
|-
 +
|KLF2
 +
|Oncogene/Tumor Suppressor
 +
|context dependent<ref name=":8" />
 +
|13-16%
 +
|-
 +
|CDKN1B
 +
|Tumor Suppressor
 +
|LOF
 +
|10-16%
 +
|-
 +
|ARID1A
 +
|Tumor Suppressor
 +
|LOF
 +
|4-5%
 
|-
 
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
+
|KMT2C
!'''Diagnostic Significance (Yes, No or Unknown)'''
+
|Tumor Suppressor
!Prognostic Significance (Yes, No or Unknown)
+
|LOF
!Therapeutic Significance (Yes, No or Unknown)
+
|15%
!Notes
 
 
|-
 
|-
|EXAMPLE: TP53; Variable LOF mutations
+
|CREBBP
 +
|Tumor Suppressor
 +
|LOF
 +
|5-6%
 +
|}
  
EXAMPLE:
 
  
EGFR; Exon 20 mutations
+
<sup>‡</sup>Specific mutations in these genes can be found in [https://www.cbioportal.org/ cBioPortal] and [https://cancer.sanger.ac.uk/cosmic COSMIC].
  
EXAMPLE: BRAF; Activating mutations
+
'''*'''The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain.  These seem to be more similar molecularly and clinically to [[HAEM5:Splenic B-cell lymphoma/leukaemia with prominent nucleoli|HCLv]].
|EXAMPLE: TSG
 
|EXAMPLE: 20% (COSMIC)
 
  
EXAMPLE: 30% (add Reference)
+
*BRAF and MAP2K1 activating mutations are mutually exclusive
|EXAMPLE: IDH1 R123H
+
*BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
|EXAMPLE: EGFR amplification
+
*BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported<ref name=":9" />
|
+
*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10" /> and instead harbor MAP2K1 mutations in most cases<ref name=":11" />
|
 
|
 
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
|}
 
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 
  
  
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{| class="wikitable"
 
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|-
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|KLF2
 
|KLF2
 
|Oncogene/Tumor Suppressor
 
|Oncogene/Tumor Suppressor
|context dependent<ref>{{Cite journal|last=Wang|first=Chunmei|last2=Li|first2=Liang|last3=Duan|first3=Qiuhui|last4=Wang|first4=Qingqing|last5=Chen|first5=Jinlian|date=2017|title=Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling|url=https://www.ncbi.nlm.nih.gov/pubmed/29245984|journal=Oncotarget|volume=8|issue=59|pages=100358–100370|doi=10.18632/oncotarget.22229|issn=1949-2553|pmc=5725026|pmid=29245984}}</ref>
+
|context dependent<ref name=":8">{{Cite journal|last=Wang|first=Chunmei|last2=Li|first2=Liang|last3=Duan|first3=Qiuhui|last4=Wang|first4=Qingqing|last5=Chen|first5=Jinlian|date=2017|title=Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling|url=https://www.ncbi.nlm.nih.gov/pubmed/29245984|journal=Oncotarget|volume=8|issue=59|pages=100358–100370|doi=10.18632/oncotarget.22229|issn=1949-2553|pmc=5725026|pmid=29245984}}</ref>
 
|13-16%
 
|13-16%
 
|-
 
|-
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*BRAF and MAP2K1 activating mutations are mutually exclusive
 
*BRAF and MAP2K1 activating mutations are mutually exclusive
 
*BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
 
*BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
*BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported<ref>{{Cite journal|last=Tschernitz|first=Sebastian|last2=Flossbach|first2=Lucia|last3=Bonengel|first3=Margrit|last4=Roth|first4=Sabine|last5=Rosenwald|first5=Andreas|last6=Geissinger|first6=Eva|date=2014|title=Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24433452|journal=British Journal of Haematology|volume=165|issue=4|pages=529–533|doi=10.1111/bjh.12735|issn=1365-2141|pmid=24433452}}</ref>
+
*BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported<ref name=":9">{{Cite journal|last=Tschernitz|first=Sebastian|last2=Flossbach|first2=Lucia|last3=Bonengel|first3=Margrit|last4=Roth|first4=Sabine|last5=Rosenwald|first5=Andreas|last6=Geissinger|first6=Eva|date=2014|title=Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24433452|journal=British Journal of Haematology|volume=165|issue=4|pages=529–533|doi=10.1111/bjh.12735|issn=1365-2141|pmid=24433452}}</ref>
*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref>{{Cite journal|last=Xi|first=Liqiang|last2=Arons|first2=Evgeny|last3=Navarro|first3=Winnifred|last4=Calvo|first4=Katherine R.|last5=Stetler-Stevenson|first5=Maryalice|last6=Raffeld|first6=Mark|last7=Kreitman|first7=Robert J.|date=2012|title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/22210875|journal=Blood|volume=119|issue=14|pages=3330–3332|doi=10.1182/blood-2011-09-379339|issn=1528-0020|pmc=3321859|pmid=22210875}}</ref> and instead harbor MAP2K1 mutations in most cases<ref>{{Cite journal|last=Waterfall|first=Joshua J.|last2=Arons|first2=Evgeny|last3=Walker|first3=Robert L.|last4=Pineda|first4=Marbin|last5=Roth|first5=Laura|last6=Killian|first6=J. Keith|last7=Abaan|first7=Ogan D.|last8=Davis|first8=Sean R.|last9=Kreitman|first9=Robert J.|date=2014|title=High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24241536|journal=Nature Genetics|volume=46|issue=1|pages=8–10|doi=10.1038/ng.2828|issn=1546-1718|pmc=3905739|pmid=24241536}}</ref>
+
*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10">{{Cite journal|last=Xi|first=Liqiang|last2=Arons|first2=Evgeny|last3=Navarro|first3=Winnifred|last4=Calvo|first4=Katherine R.|last5=Stetler-Stevenson|first5=Maryalice|last6=Raffeld|first6=Mark|last7=Kreitman|first7=Robert J.|date=2012|title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/22210875|journal=Blood|volume=119|issue=14|pages=3330–3332|doi=10.1182/blood-2011-09-379339|issn=1528-0020|pmc=3321859|pmid=22210875}}</ref> and instead harbor MAP2K1 mutations in most cases<ref name=":11">{{Cite journal|last=Waterfall|first=Joshua J.|last2=Arons|first2=Evgeny|last3=Walker|first3=Robert L.|last4=Pineda|first4=Marbin|last5=Roth|first5=Laura|last6=Killian|first6=J. Keith|last7=Abaan|first7=Ogan D.|last8=Davis|first8=Sean R.|last9=Kreitman|first9=Robert J.|date=2014|title=High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24241536|journal=Nature Genetics|volume=46|issue=1|pages=8–10|doi=10.1038/ng.2828|issn=1546-1718|pmc=3905739|pmid=24241536}}</ref>
  
 
</blockquote>
 
</blockquote>
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==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
 
 
{| class="wikitable sortable"
 
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|-
 
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
+
!Molecular feature!!Pathway!!Pathophysiologic outcome
 
|-
 
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|BRAF & MAP2K1 activating mutations
|EXAMPLE: MAPK signaling
+
(IGH-BRAF fusion, 1 report<ref name=":3" />)
|EXAMPLE: Increased cell growth and proliferation
+
|MAPK signaling
 +
|Increased cell growth and proliferation
 
|-
 
|-
|EXAMPLE: CDKN2A; Inactivating mutations
+
|CDKN1B inactivating mutations
|EXAMPLE: Cell cycle regulation
+
(IGH-CCND1 fusion, 1 report<ref name=":4" />)
|EXAMPLE: Unregulated cell division
+
|Cell cycle regulation
 +
|Unregulated cell division
 
|-
 
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|KMT2C & ARID1A inactivating mutaitons
|EXAMPLE:  Histone modification, chromatin remodeling
+
|Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
+
|Abnormal gene expression program
 
|}
 
|}
  
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!Molecular feature
 
!Molecular feature
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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
 
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
  
'''
+
<br />
  
 
==Notes==
 
==Notes==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>''Citation of this Page'': “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases H]]
+
[[Category:HAEM5]]
 +
[[Category:DISEASE]]
 +
[[Category:Diseases H]]

Latest revision as of 17:27, 6 September 2024


Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Hairy Cell Leukemia.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

  • Michael Lack, DO, Shivani Golem, PhD FACMG

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Mature B-cell neoplasms
Type Splenic B-cell lymphomas and leukaemias
Subtype(s) Hairy cell leukaemia

Definition / Description of Disease

  • Hairy cell leukemia (HCL) is a rare indolent neoplasm of B-cell origin seen mostly in adults
  • Name derives from the the hair-like projections of the cytoplasm that surround the cells
  • Hairy cells most closely resemble mature lymphoid cells
  • Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections
  • Most respond well to monotherapy with a purine analog or interferon alpha

Synonyms / Terminology

  • Leukemic reticuloendotheliosis

Epidemiology / Prevalence

  • Incidence (age adjusted) ~ 0.3/100,000
  • 2% of lymphoid leukemias
  • Median age: 58 years, rarely in patients in their 20s
  • Males:Females: 4:1
  • Whites >> Blacks
  • 78% to 92% 5yr survival


editUnassigned References
The following referenees were placed in the header. Please place them into the appropriate locations in the text.

[1][2]

Clinical Features

Signs and Symptoms
  • Asymptomatic (incidental finding on complete blood counts)
  • B-symptoms (weight loss, fever, night sweats)
  • Fatigue
  • Splenic enlargement and discomfort
  • Recurrent infections
  • Lymphadenopathy (rare)
Laboratory Findings Pancytopenia (monocytopenia is characteristic)

Lymphocytosis (low level)


editv4:Clinical Features
The content below was from the old template. Please incorporate above.


Signs & Symptoms

  • Asymptomatic (incidental finding on complete blood counts)
  • B-symptoms (weight loss, fever, night sweats)
  • Fatigue
  • LUQ pain (splenomegaly)
  • Lymphadenopathy (uncommon)

Laboratory findings

  • Cytopenias
  • Monocytopenia
  • Lymphocytosis (low level)
editUnassigned References
The following referenees were placed in the header. Please place them into the appropriate locations in the text.

[1][3]

Sites of Involvement

  • Spleen (red pulp)
  • Bone marrow
  • Liver
  • Blood (small number)
editUnassigned References
The following referenees were placed in the header. Please place them into the appropriate locations in the text.

[1][3]

Morphologic Features

  • Small lymphoid cells
  • Abundant pale blue-grey lacey cytoplasm
  • Ovoid nuclei ± indentation or folding
  • Inconspicuous nucleoli
  • Circumferential hairy projections (smear preparations)
  • "Fried egg" appearance of cells (tissue sections)
  • Marrow (reticulin) fibrosis


editUnassigned References
The following referenees were placed in the header. Please place them into the appropriate locations in the text.

[1][3]

Immunophenotype

Finding Marker
Positive (B-cell lineage markersl) CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
Positive CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
Negative CD5, CD10 (10-20% may be positive), CD23, CD27


editv4:Immunophenotype
The content below was from the old template. Please incorporate above.


Finding Marker
Positive (B-cell lineage markers) CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
Positive CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
Negative CD5, CD10 (10-20% may be positive), CD23, CD27


editUnassigned References
The following referenees were placed in the header. Please place them into the appropriate locations in the text.

[1][3]

Chromosomal Rearrangements (Gene Fusions)

  • No consistent gene fusions
  • Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL[4]
  • Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL[5]
editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.
  • No consistent gene fusions
  • Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL[4]
  • Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL[5]


editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)
Alteration Clinical Significance Note
BRAF p.Val600Glu Predictive* vemurafenib for 2nd line; vemurafenib ± rituximab for 3rd line (NCCN, v 1.2020, pg. HCL-A)[6]
BRAF p.Val600Glu Diagnostic May be useful when immunophenotype is equivocal; Excludes HCLv
MAP2K1 Predictive Certain mutations may confer sensitivity to ERK inhibitors
IGHV4-34 utilization Predictive Reduced response to purine analogs[7]
IGHV4-34 utilization Prognostic Less favorable prognosis[7]

*Not all BRAF mutations confer sensitivity to BRAF inhibitors, even if they are activating mutations[8].

Individual Region Genomic Gain / Loss / LOH

chromosome[9][10] Alteration Consequence Prevalence
14q22-32 Heterozygous deletion Uncertain 33%
7q Heterozygous deletion LOH of BRAF p.Val600Glu 9-21%
13q Deletion Loss of RB1, miR-15a, and miR-16-1 6%
5 Gain Uncertain 9-15%
editv4:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.
  • Recurrent gains and losses were found to be absent in HCLs from Chinese patients[11]
chromosome[9][10] Alteration Consequence Prevalence
14q22-32 Heterozygous deletion Uncertain 33%
7q Heterozygous deletion LOH of BRAF p.Val600Glu 9-21%
13q Deletion Loss of RB1, miR-15a, and miR-16-1 6%
5 Gain Uncertain 9-15%

Characteristic Chromosomal Patterns

IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%[7] of HCL but has predictive and prognostic implications[12].

editv4:Characteristic Chromosomal Aberrations / Patterns
The content below was from the old template. Please incorporate above.
  • IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%[7] of HCL but has predictive and prognostic implications[12].

Gene Mutations (SNV / INDEL)

Gene Oncogene/Tumor Suppressor/Other Presumed Mechanism

(LOF/GOF/Other)

Prevalence[1]
BRAF Oncogene GOF 70-100%*
MAP2K1 Oncogene GOF 0-22%*
TP53 Tumor Suppressor LOF 2-28%
KLF2 Oncogene/Tumor Suppressor context dependent[13] 13-16%
CDKN1B Tumor Suppressor LOF 10-16%
ARID1A Tumor Suppressor LOF 4-5%
KMT2C Tumor Suppressor LOF 15%
CREBBP Tumor Suppressor LOF 5-6%


Specific mutations in these genes can be found in cBioPortal and COSMIC.

*The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain. These seem to be more similar molecularly and clinically to HCLv.

  • BRAF and MAP2K1 activating mutations are mutually exclusive
  • BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
  • BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported[14]
  • HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations[15] and instead harbor MAP2K1 mutations in most cases[16]


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.
Gene Oncogene/Tumor Suppressor/Other Presumed Mechanism

(LOF/GOF/Other)

Prevalence[1]
BRAF Oncogene GOF 70-100%*
MAP2K1 Oncogene GOF 0-22%*
TP53 Tumor Suppressor LOF 2-28%
KLF2 Oncogene/Tumor Suppressor context dependent[13] 13-16%
CDKN1B Tumor Suppressor LOF 10-16%
ARID1A Tumor Suppressor LOF 4-5%
KMT2C Tumor Suppressor LOF 15%
CREBBP Tumor Suppressor LOF 5-6%

Specific mutations in these genes can be found in cBioPortal and COSMIC.

*The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain. These seem to be more similar molecularly and clinically to HCLv.

  • BRAF and MAP2K1 activating mutations are mutually exclusive
  • BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
  • BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported[14]
  • HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations[15] and instead harbor MAP2K1 mutations in most cases[16]

Epigenomic Alterations

  • Altered epigenetic regulation is expected due to alterations in KMT2C and ARID1A in a subset of HCLs
    • KMT2C is a histone methyltransferase
    • ARID1A is a SWI/SNF family member

Genes and Main Pathways Involved

Molecular feature Pathway Pathophysiologic outcome
BRAF & MAP2K1 activating mutations

(IGH-BRAF fusion, 1 report[4])

MAPK signaling Increased cell growth and proliferation
CDKN1B inactivating mutations

(IGH-CCND1 fusion, 1 report[5])

Cell cycle regulation Unregulated cell division
KMT2C & ARID1A inactivating mutaitons Histone modification, chromatin remodeling Abnormal gene expression program
editv4:Genes and Main Pathways Involved
The content below was from the old template. Please incorporate above.
Molecular feature Pathway Pathophysiologic outcome
BRAF & MAP2K1 activating mutations

(IGH-BRAF fusion, 1 report[4])

MAPK signaling Increased cell growth and proliferation
CDKN1B inactivating mutations

(IGH-CCND1 fusion, 1 report[5])

Cell cycle regulation Unregulated cell division
KMT2C & ARID1A inactivating mutaitons Histone modification, chromatin remodeling Abnormal gene expression program

Genetic Diagnostic Testing Methods

  • Morphology and immunophenotyping (IHC or flow cytometry) are adequate for diagnosis in nearly all cases
  • BRAF p.Val600Glu testing may be useful diagnostically in rare situations where clinicopathologic findings are equivocal
  • BRAF p.Val600Glu may be detected by IHC using a mutant-specific antibody[17][18] or various molecular methods (NGS, real-time PCR, massARRAY, etc.)
  • The mutant-specific antibody does not detect other BRAF mutations
  • BRAF p.Val600Glu and Non-p.Val600Glu mutations and MAP2K1 mutations can be interrogated with NGS in a single assay[1]
  • IGHV4-34 utilization can be detected by NGS

Familial Forms

  • Familial association has been reported in several case reports
  • Some linked to various HLA type[19]
  • Others to familial occupation[20]

Additional Information

  • N/A

Links

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Maitre, Elsa; et al. (2019). "Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment". American Journal of Hematology. 94 (12): 1413–1422. doi:10.1002/ajh.25653. ISSN 1096-8652. PMID 31591741.
  2. Lr, Teras; et al. (2016). "2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes". PMID 27618563.
  3. 3.0 3.1 3.2 3.3 Grever, Michael R.; et al. (2017). "Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia". Blood. 129 (5): 553–560. doi:10.1182/blood-2016-01-689422. ISSN 0006-4971. PMC 5290982. PMID 27903528.CS1 maint: PMC format (link)
  4. 4.0 4.1 4.2 4.3 Thompson, Ella R.; et al. (2020). "Detection of an IGH-BRAF fusion in a patient with BRAF Val600Glu negative hairy cell leukemia". Leukemia & Lymphoma: 1–3. doi:10.1080/10428194.2020.1753045. ISSN 1029-2403. PMID 32319330 Check |pmid= value (help).
  5. 5.0 5.1 5.2 5.3 Rahman, Zaid Abdel; et al. (2020). "Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation". Leukemia Research Reports. 13: 100197. doi:10.1016/j.lrr.2020.100197. ISSN 2213-0489. PMC 7096740 Check |pmc= value (help). PMID 32257795 Check |pmid= value (help).
  6. National Comprehensive Cancer Network (January 2020). "NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia" (PDF).CS1 maint: display-authors (link)
  7. 7.0 7.1 7.2 7.3 Arons, Evgeny; et al. (2009). "VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy". Blood. 114 (21): 4687–4695. doi:10.1182/blood-2009-01-201731. ISSN 1528-0020. PMC 2780305. PMID 19745070.
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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia.