Difference between revisions of "HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement"

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(Created page with "{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with PDGFRB rearrangement}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote class='...")
 
 
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{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with PDGFRB rearrangement}}
 
{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with PDGFRB rearrangement}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
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[[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 2023-11-03. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement]].
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<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:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement]].
 
}}</blockquote>
 
}}</blockquote>
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<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>
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==Primary Author(s)*==
 
==Primary Author(s)*==
  
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__TOC__
 
__TOC__
  
==Cancer Category/Type==
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==WHO Classification of Disease==
  
Myeloid Neoplasms/Acute myeloid leukemia
+
{| class="wikitable"
 
+
!Structure
==Cancer Sub-Classification / Subtype==
+
!Disease
 
+
|-
Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement
+
|Book
 +
|Haematolymphoid Tumours (5th ed.)
 +
|-
 +
|Category
 +
|Myeloid proliferations and neoplasms
 +
|-
 +
|Family
 +
|Myeloid/lymphoid neoplasms
 +
|-
 +
|Type
 +
|Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangement
 +
|-
 +
|Subtype(s)
 +
|Myeloid/lymphoid neoplasm with PDGFRB rearrangement
 +
|}
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
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==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>
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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>
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
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|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
  
EXAMPLE B-symptoms (weight loss, fever, night sweats)
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<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
  
EXAMPLE Fatigue
+
<span class="blue-text">EXAMPLE:</span> Fatigue
  
EXAMPLE Lymphadenopathy (uncommon)
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<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
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|<span class="blue-text">EXAMPLE:</span> Cytopenias
  
EXAMPLE Lymphocytosis (low level)
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<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
|}
 
|}
  
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==Immunophenotype==
 
==Immunophenotype==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
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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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||EXAMPLE CD1
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|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
 
|-
 
|-
|Positive (subset)||EXAMPLE CD2
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|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
 
|-
 
|-
|Negative (universal)||EXAMPLE CD3
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|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
 
|-
 
|-
|Negative (subset)||EXAMPLE CD4
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|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
 
|}
 
|}
  
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
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|<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 30% (add reference)
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<span class="blue-text">EXAMPLE:</span> 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
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).
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</blockquote>
 
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
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==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>
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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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
7
 
7
|EXAMPLE Loss
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|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr7
 
chr7
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|Yes
 
|Yes
 
|No
 
|No
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
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).
 
|-
 
|-
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
8
 
8
|EXAMPLE Gain
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|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr8
 
chr8
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|No
 
|No
 
|No
 
|No
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
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==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>
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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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|No
 
|No
 
|No
 
|No
|EXAMPLE:
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|<span class="blue-text">EXAMPLE:</span>
  
 
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).
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t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.
 
t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.
 
</blockquote>
 
</blockquote>
==Gene Mutations (SNV/INDEL)==
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==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 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>
+
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>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE: TP53; Variable LOF mutations
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|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
  
EXAMPLE:
+
<span class="blue-text">EXAMPLE:</span>
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
EXAMPLE: BRAF; Activating mutations
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<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|EXAMPLE: TSG
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|<span class="blue-text">EXAMPLE:</span> TSG
|EXAMPLE: 20% (COSMIC)
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|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
  
EXAMPLE: 30% (add Reference)
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<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|EXAMPLE: IDH1 R123H
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|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|EXAMPLE: EGFR amplification
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|<span class="blue-text">EXAMPLE:</span> EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<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.
 
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.
  
 +
 +
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
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Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins<ref>Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.</ref>.
 +
 +
</blockquote>
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
  
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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>
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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>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
+
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|-
 
|-
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
+
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
+
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
 
|}
 
|}
  
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==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'': “Myeloid/lymphoid neoplasm with PDGFRB rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRB_rearrangement</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “Myeloid/lymphoid neoplasm with PDGFRB rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRB_rearrangement</nowiki>.
==Other Sections==
 
Gene Mutations
 
 
Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins<ref>Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.</ref>.
 
 
 
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
 
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]

Latest revision as of 17:21, 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:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement.

(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)*

Christopher Sullivan, MD, MPH and Daynna J. Wolff, PhD

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Myeloid/lymphoid neoplasms
Type Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangement
Subtype(s) Myeloid/lymphoid neoplasm with PDGFRB rearrangement

Definition / Description of Disease

Gene fusions with PDGFRB were first described by Golub et al. in 1994 in a patient with features consistent with chronic myelomonocytic leukemia (CMML)[1]. Since that time, over 20 fusion partners have been described[2][3]. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRB are rare, accounting for less than 2% of all myelodysplastic/myeloproliferative neoplasms (MDS/MPN)[3].

Synonyms / Terminology

Chronic myelomonocytic leukemia with eosinophilia associated with t(5;12); myeloid neoplasms with PDGFRB rearrangement; myeloid neoplasms associated with PDGFRB rearrangement.

Epidemiology / Prevalence

This neoplasm is considerably more common in men than in women (male-to-female ratio: 2:1) and occurs over a wide age range (8-72 years), with peak incidence in middle-aged adults and a median age of onset in the late 40s[4].

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete 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.

Patients typically present with splenomegaly; hepatomegaly is less frequent. Lymphadenopathy may also be seen. Skin and cardiac infiltration may be present at diagnosis with resulting cardiac damage. Serum tryptase levels may be elevated.

Sites of Involvement

MPN associated with t(5;12)(q32;p13.2) is a multisystem disorder. The peripheral blood and bone marrow are always involved. The spleen is enlarged in most cases. Tissue infiltration by eosinophils and cytokine release, humoral factors, or granule contents by eosinophils can contribute to tissue damage in several organs[5].

Morphologic Features

In patients with abnormalities of PDGFRB, peripheral blood and bone marrow is almost always involved. Leukocytosis is typical with monocytosis and eosinophilia. Rarely, basophilia is also prominent. Anemia and thrombocytopenia may also be present. Overall, the features are typically suggestive of CMML with eosinophilia; however, some patients present with features more in keeping with aCML or CEL. Rarely, they present with features of ALL, AML, and juvenile myelomonocytic leukemia (JMML)[6].

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete 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.

The mast cells show expression of CD2 and CD25, which is also found in most mast cell disease.

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.
Translocation Fusion Gene Hematological Diagnosis
t(5;12)(q32;p13.2) ETV6-PDGFRB CMML with eosinophilia, CEL
t(1;3;5)(q36;q11.2) WDR48-PDGFRB CEL
der(1)t(1;5)(p34;q32),

der(5)t(1;5)(p34;q15),

der(11)ins(11;5)(p13;q15q32)

CAPRIN1-PDGFRB CEL
t(1;5)(q21.3;q32) TPM3-PDGFRB
t(1;5)(q21.2;q32) PDE4DIP-PDGFRB MDS/MPN with eosinophilia
t(2;5)(p16.2;q32) SPTBN1-PDGFRB
t(4;5;5)(q21.2;q31;q32) PRKG2-PDGFRB Chronic basophilia leukemia
t(3;5)(p22.2;q32) GOLGA4-PDGFRB CEL or aCML with eosinophilia
Cryptic interstitial deletion of 5q TNIP1-PDGFRB CEL with thrombocytosis
t(5;7)(q32;q11.2) HIP1-PDGFRB CMML with eosinophilia
t(5;7)(q32;p14.1) HECW1-PDGFRB JMML
t(5;9)(q32;p24.3) KANK1-PDGFRB Essential thrombocythemia without eosinophilia
t(5;10)(q32;q21.2) CCDC6-PDGFRB aCML with eosinophilia or MPN with eosinophilia
Uninformative SART3-PDGFRB MPN with eosniophilia
t(5;12)(q32;q24.1) GIT2-PDGFRB CEL
t(5;12)(q32;p13.3) ERC1-PDGFRB AML without eosniophilia
t(5;12)(q32;p13.1) BIN2-PDGFRB aCML with eosinophilia
t(5;14)(q32;q22.1) NIN-PDGFRB Ph-negative CML (13% eosinophils)
t(5;14)(q32;q32.1) CCDC88C-PDGFRB CMML with eosinophilia
t(5;15)(q32;q15.3) TP53BP1-PDGFRB Ph-negative CML with prominent eosinophilia
t(5;16)(q32;p13.1) NDE1-PDGFRB CMML
t(5;17)(q32;p13.2) RABEP1-PDGFRB CMML
t(5;17)(q32;p11.2) SPECC1-PDGFRB JMML
t(5;17)(q32;q11.2) MYO18A-PDGFRB MPN with eosinophilia
t(5;17)(q32;q21.3) COL1A1-PDGFRB MDS or MPN with eosinophilia
t(5;20)(q32;p11.2) DTD1-PDGFRB CEL


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)

Before the introduction of imatinib therapy, the median survival was <2 years. Most patients are now known to have excellent morphologic and molecular response to therapy with a recent study showing a 10-year overall survival of 90%[7]. Furthermore, earlier diagnosis due to recognition of this entity will result in earlier initiation of appropriate therapy, preventing cardiac damage and blast phase. Primary and secondary resistance is uncommon; however, initial response typically occurs within 2 months, and if not seen by 3 months, consideration of another therapy is suggested. Whether or not therapy can be stopped in patients with long term molecular remission is still up for debate, with a recent article citing one patient in remission 4 years after therapy cessation[8].

Individual Region Genomic Gain / Loss / LOH

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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).

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. Do not delete table.)

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
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t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.

Gene Mutations (SNV / INDEL)

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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)
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Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins[9].

Epigenomic Alterations

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Genes and Main Pathways Involved

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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
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PDGFRB encodes a plasma membrane-spanning receptor with five extracellular immunoglobulin-like loops for ligand binding and a split intracellular tyrosine kinase domain. Signal transduction is very similar, with ligand binding inducing dimerization and autophosphorylation of the tyrosine kinase. In addition to its role in embryonic development, PDGFRB mediates chemotactic responses of monocytes, macrophages, and platelets to inflammatory processes. Overexpression has been implicated in solid tumors, such as medulloblastoma and chordoma[10].

Genetic Diagnostic Testing Methods

FISH (break-apart FISH with a PDGFRB probe) is indicated in all patients with a presumptive diagnosis of MPN with a 5q31-33 breakpoint, in particular if there is eosinophilia. However, FISH analysis does not always demonstrate rearrangement of PDGFRB even when such rearrangement is detectable on Southern blot anaylsis[4]. Molecular analysis is not indicated when no 5q31-33 breakpoint is found by conventional cytogenetic analysis, because almost all cases reported to date in which 20 metaphases were available for examination have had a cytogenetically detectable abnormality[5].

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

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Links

PDGFRB

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. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor-beta to a novel Ets-like gene, Tel, in chronic myelomonocytic leukemia with t(512) chromosomal translocation. Cell. 1994;77(2):307–16.
  2. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 .Genes as a therapeutic target of imatinib in idiopathic Hypereosinophilic syndrome. N Engl J Med. 2003;348(13):1201–14.
  3. 3.0 3.1 Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN. Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015;144(3):377–92.
  4. 4.0 4.1 Steer, E. J., & Cross, N. C. (2002). Myeloproliferative disorders with translocations of chromosome 5q31–35: role of the platelet-derived growth factor receptor Beta. Acta haematologica, 107(2), 113-122.
  5. 5.0 5.1 Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours. Lyon, France: IARC; 2008
  6. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 .Genes as a therapeutic target of imatinib in idiopathic Hypereosinophilic syndrome. N Engl J Med. 2003;348(13):1201–14.
  7. Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, et al. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014;123(23):3574–7.
  8. Cerrano M, Crisà E, Gottardi E, Aguzzi C, Boccadoro M, Ferrero D. Long-term therapy-free remission in a patient with platelet-derived growth factor receptor beta (PDGFRB)- rearranged myeloproliferative neoplasm. Am J Hematol. 2016;91(9):E353.
  9. Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.
  10. Chang, C. C., & Ohgami, R. S. (Eds.). (2018). Precision molecular pathology of myeloid neoplasms. Springer.

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: “Myeloid/lymphoid neoplasm with PDGFRB rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRB_rearrangement.