Difference between revisions of "HAEM5:Acute undifferentiated leukaemia"

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search
VisualWikitext
[checked revision][checked revision]
(Undo revision 14811 by Bailey.Glen (talk))
Tag: Undo
Line 1: Line 1:
 
{{DISPLAYTITLE:Acute undifferentiated leukaemia}}
 
{{DISPLAYTITLE:Acute undifferentiated leukaemia}}
−
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
+
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
Line 7: Line 7:
 
}}</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 nearby 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>
+
<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). 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)*==
Line 39: Line 39:
 
==Clinical Features==
 
==Clinical Features==
  
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
+
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'''
−
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
  
−
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
+
EXAMPLE B-symptoms (weight loss, fever, night sweats)
  
−
<span class="blue-text">EXAMPLE:</span> Fatigue
+
EXAMPLE Fatigue
  
−
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
+
EXAMPLE Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|<span class="blue-text">EXAMPLE:</span> Cytopenias
+
|EXAMPLE Cytopenias
  
−
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
+
EXAMPLE Lymphocytosis (low level)
 
|}
 
|}
  
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
  
 
In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation<ref name=":2">{{Cite journal|displayauthors=1|last=Heesch|first=Sandra|last2=Neumann|first2=Martin|last3=Schwartz|first3=Stefan|last4=Bartram|first4=Isabelle|last5=Schlee|first5=Cornelia|last6=Burmeister|first6=Thomas|last7=Hänel|first7=Matthias|last8=Ganser|first8=Arnold|last9=Heuser|first9=Michael|date=2013|title=Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization|url=https://pubmed.ncbi.nlm.nih.gov/23412561|journal=Annals of Hematology|volume=92|issue=6|pages=747–758|doi=10.1007/s00277-013-1694-4|issn=1432-0584|pmid=23412561|via=}}</ref>. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates<ref>{{Cite journal|displayauthors=1|last=Weinberg|first=Olga K.|last2=Hasserjian|first2=Robert P.|last3=Baraban|first3=Ezra|last4=Ok|first4=Chi Young|last5=Geyer|first5=Julia T.|last6=Philip|first6=John K. S. S.|last7=Kurzer|first7=Jason H.|last8=Rogers|first8=Heesun J.|last9=Nardi|first9=Valentina|date=2019|title=Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group|url=https://pubmed.ncbi.nlm.nih.gov/31000771|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=32|issue=9|pages=1373–1385|doi=10.1038/s41379-019-0263-3|issn=1530-0285|pmid=31000771|via=}}</ref>.
 
In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation<ref name=":2">{{Cite journal|displayauthors=1|last=Heesch|first=Sandra|last2=Neumann|first2=Martin|last3=Schwartz|first3=Stefan|last4=Bartram|first4=Isabelle|last5=Schlee|first5=Cornelia|last6=Burmeister|first6=Thomas|last7=Hänel|first7=Matthias|last8=Ganser|first8=Arnold|last9=Heuser|first9=Michael|date=2013|title=Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization|url=https://pubmed.ncbi.nlm.nih.gov/23412561|journal=Annals of Hematology|volume=92|issue=6|pages=747–758|doi=10.1007/s00277-013-1694-4|issn=1432-0584|pmid=23412561|via=}}</ref>. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates<ref>{{Cite journal|displayauthors=1|last=Weinberg|first=Olga K.|last2=Hasserjian|first2=Robert P.|last3=Baraban|first3=Ezra|last4=Ok|first4=Chi Young|last5=Geyer|first5=Julia T.|last6=Philip|first6=John K. S. S.|last7=Kurzer|first7=Jason H.|last8=Rogers|first8=Heesun J.|last9=Nardi|first9=Valentina|date=2019|title=Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group|url=https://pubmed.ncbi.nlm.nih.gov/31000771|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=32|issue=9|pages=1373–1385|doi=10.1038/s41379-019-0263-3|issn=1530-0285|pmid=31000771|via=}}</ref>.
Line 74: Line 74:
 
==Immunophenotype==
 
==Immunophenotype==
  
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
+
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"
Line 80: Line 80:
 
!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
+
|Positive (universal)||EXAMPLE CD1
 
|-
 
|-
−
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
+
|Positive (subset)||EXAMPLE CD2
 
|-
 
|-
−
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
+
|Negative (universal)||EXAMPLE CD3
 
|-
 
|-
−
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
+
|Negative (subset)||EXAMPLE CD4
 
|}
 
|}
  
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
  
 
Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.
 
Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.
Line 131: Line 131:
 
!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
−
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
+
EXAMPLE 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
−
|<span class="blue-text">EXAMPLE:</span>
+
|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).
 
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).
Line 142: Line 142:
 
 
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
  
 
NA
 
NA
Line 148: Line 148:
  
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|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 159: Line 159:
 
==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. Do not delete table.'') </span>
+
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 sortable"
 
{| class="wikitable sortable"
Line 169: Line 169:
 
!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
7
 
7
−
|<span class="blue-text">EXAMPLE:</span> Loss
+
|EXAMPLE Loss
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr7
 
chr7
Line 182: Line 182:
 
|Yes
 
|Yes
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|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).
 
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).
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
8
 
8
−
|<span class="blue-text">EXAMPLE:</span> Gain
+
|EXAMPLE Gain
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr8
 
chr8
Line 199: Line 199:
 
|No
 
|No
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
  
 
NA
 
NA
Line 210: Line 210:
 
==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. Do not delete table.'')</span>
+
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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 220: Line 220:
 
!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
Line 226: Line 226:
 
|No
 
|No
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE:
  
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
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=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
  
 
AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities<ref name=":2" />.  
 
AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities<ref name=":2" />.  
Line 238: Line 238:
 
==Gene Mutations (SNV / INDEL)==
 
==Gene Mutations (SNV / INDEL)==
  
−
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 as 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. Do not delete table.'') </span>
+
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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 248: Line 248:
 
!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
+
|EXAMPLE: TP53; Variable LOF mutations
  
−
<span class="blue-text">EXAMPLE:</span>
+
EXAMPLE:
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
−
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
+
EXAMPLE: BRAF; Activating mutations
−
|<span class="blue-text">EXAMPLE:</span> TSG
+
|EXAMPLE: TSG
−
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|EXAMPLE: 20% (COSMIC)
  
−
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
+
EXAMPLE: 30% (add Reference)
−
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
+
|EXAMPLE: IDH1 R123H
−
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
+
|EXAMPLE: EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
−
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
+
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
Line 270: Line 270:
  
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
  
 
PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited.
 
PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited.
Line 283: Line 283:
 
==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. Do not delete table.'')</span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
+
|EXAMPLE: BRAF and MAP2K1; Activating mutations
−
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
+
|EXAMPLE: MAPK signaling
−
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
+
|EXAMPLE: Increased cell growth and proliferation
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
+
|EXAMPLE: CDKN2A; Inactivating mutations
−
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+
|EXAMPLE: Cell cycle regulation
−
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
+
|EXAMPLE: Unregulated cell division
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
+
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
−
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
+
|EXAMPLE:  Histone modification, chromatin remodeling
−
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
+
|EXAMPLE:  Abnormal gene expression program
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
  
 
Overexpression of BAALC, ERG, and MN1<ref name=":0" />.  
 
Overexpression of BAALC, ERG, and MN1<ref name=":0" />.  

Revision as of 14:53, 6 September 2024

Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Undifferentiated 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). 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)*

Amelia Nakanishi, MD and Shashi Shetty, PhD

Cancer Category / Type

Hematologic malignancy/ Acute leukemia

Cancer Sub-Classification / Subtype

Acute Leukemias of Ambiguous Lineage (WHO 2017)/ Acute Undifferentiated Leukemia (AUL)

Definition / Description of Disease

An acute leukemia with blasts that are immunophenotypically ambiguous for any one hematopoietic lineage. AUL is a diagnosis of exclusion that is incompatible with the presence of features that meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

To support an undifferentiated phenotype, AUL requires an immunophenotypic work up that “excludes unusual lineages such as plasmacytoid dendritic cell precursors, natural killer precursors, basophils, and non-hematologic cells”[1].

Synonyms / Terminology

Blast cell leukemia, stem cell leukemia, stem cell acute leukemia, undifferentiated leukemia.

Epidemiology / Prevalence

Very rare; precise frequency unknown.

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table)

Signs and Symptoms EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Fatigue

EXAMPLE Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE Cytopenias

EXAMPLE Lymphocytosis (low level)


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

In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation[2]. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates[3].

In children, based on limited clinical information in the literature, AUL has been associated with a poor prognosis[4].

Sites of Involvement

Bone marrow and peripheral blood. AUL is so rare, it is unknown if there is a pattern of other sites of involvement.

Morphologic Features

AUL blast morphology is bland and non-specific. Cytoplasmic granulation and disease defining morphology are absent.

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table)

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4


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

Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.

Positive (universal) Precursor stage: HLA-DR, CD34, and/or CD38, CD117, CD133 [5]
Positive (subset) TdT

CD7 (weak positivity) see below.

Negative (universal) Myeloid: MPO

Monocytic: NSE, CD11c, Cd14, CD64, lysozyme, Cd4, CD11b, CD36, NG2 homologue

T cell: cCD3

B cell: cCD22, cCD79a, strong CD19

Megakaryocytic: CD41, CD61, CD42, CD235a

Negative (subset) NA

Additional Description: Blasts are generally positive for  HLA-DR, CD34, and/or CD38.

-CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia[1].

-See HAEM4:Acute Leukemias of Ambiguous Lineage for assigning lineage assignment.

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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).


editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.

NA


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)

There is evidence that the genes associated with poor prognosis in acute leukemias, BAALC, ERG, and MN1, are also overexpressed in AUL[1].

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (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.)

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE

7

EXAMPLE Loss 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

8

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).

editv4:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.

NA

Characteristic Chromosomal Patterns

Put your text here (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)

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

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns
The content below was from the old template. Please incorporate above.

AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities[2].

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (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.)

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.

PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited.

Other Mutations

NA

Epigenomic Alterations

Unknown

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations EXAMPLE:  Histone modification, chromatin remodeling EXAMPLE:  Abnormal gene expression program
editv4:Genes and Main Pathways Involved
The content below was from the old template. Please incorporate above.

Overexpression of BAALC, ERG, and MN1[1].

Genetic Diagnostic Testing Methods

Morphology, immunohistochemistry, cytochemistry, flow cytometry, cytogenetics, and next generation sequencing.

Familial Forms

Unknown

Additional Information

Although AUL and AML with minimal differentiation are both rare diagnoses, they have similar patient demographics and clinical courses. AUL and AML with minimal differentiation have different molecular abnormalities[2].

Links

HAEM4:Acute Leukemias of Ambiguous Lineage

HAEM5:Mixed-phenotype acute leukaemia, B/myeloid

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 Borowitz MJ, et al., (2017). Acute leukaemias of ambiguous lineage, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p182.
  2. ↑ 2.0 2.1 2.2 Heesch, Sandra; et al. (2013). "Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization". Annals of Hematology. 92 (6): 747–758. doi:10.1007/s00277-013-1694-4. ISSN 1432-0584. PMID 23412561.
  3. ↑ Weinberg, Olga K.; et al. (2019). "Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 32 (9): 1373–1385. doi:10.1038/s41379-019-0263-3. ISSN 1530-0285. PMID 31000771.
  4. ↑ Lee, Hyun Gyung; et al. (2019). "Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome". Blood Research. 54 (1): 63–73. doi:10.5045/br.2019.54.1.63. ISSN 2287-979X. PMC 6439300. PMID 30956966.
  5. ↑ Hoffman R, et al., (2018) Hematology, basic principles and practice, 7th edition. Elsevier: Philadelphia. (clinical key excerpt)

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: “Acute undifferentiated leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Acute_undifferentiated_leukaemia.

Retrieved from "https://ccga.io/index.php?title=HAEM5:Acute_undifferentiated_leukaemia&oldid=14959"