Difference between revisions of "HAEM5:Polycythaemia vera"
Jump to navigation
Jump to search
| [unchecked revision] | [checked revision] |
Bailey.Glen (talk | contribs) |
Bailey.Glen (talk | contribs) |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
{{DISPLAYTITLE:Polycythaemia vera}} | {{DISPLAYTITLE:Polycythaemia vera}} | ||
| − | [[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= | + | <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:Polycythemia Vera (PV)]]. |
}}</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)*== | ||
| Line 14: | Line 17: | ||
__TOC__ | __TOC__ | ||
| − | == | + | ==WHO Classification of Disease== |
| − | Myeloproliferative neoplasms | + | {| class="wikitable" |
| − | + | !Structure | |
| − | + | !Disease | |
| − | + | |- | |
| − | + | |Book | |
| + | |Haematolymphoid Tumours (5th ed.) | ||
| + | |- | ||
| + | |Category | ||
| + | |Myeloid proliferations and neoplasms | ||
| + | |- | ||
| + | |Family | ||
| + | |Myeloproliferative neoplasms | ||
| + | |- | ||
| + | |Type | ||
| + | |Myeloproliferative neoplasms | ||
| + | |- | ||
| + | |Subtype(s) | ||
| + | |Polycythaemia vera | ||
| + | |} | ||
==Definition / Description of Disease== | ==Definition / Description of Disease== | ||
| Line 47: | Line 64: | ||
==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> | + | 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) | + | |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts) |
| − | EXAMPLE B-symptoms (weight loss, fever, night sweats) | + | <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) | + | <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon) |
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| − | |EXAMPLE Cytopenias | + | |<span class="blue-text">EXAMPLE:</span> Cytopenias |
| − | EXAMPLE Lymphocytosis (low level) | + | <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level) |
|} | |} | ||
| Line 98: | Line 115: | ||
==Immunophenotype== | ==Immunophenotype== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | 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" | ||
| Line 104: | Line 121: | ||
!Finding!!Marker | !Finding!!Marker | ||
|- | |- | ||
| − | |Positive (universal)||EXAMPLE CD1 | + | |Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1 |
|- | |- | ||
| − | |Positive (subset)||EXAMPLE CD2 | + | |Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2 |
|- | |- | ||
| − | |Negative (universal)||EXAMPLE CD3 | + | |Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3 |
|- | |- | ||
| − | |Negative (subset)||EXAMPLE CD4 | + | |Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4 |
|} | |} | ||
| Line 131: | Line 148: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC) | + | |<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) | + | <span class="blue-text">EXAMPLE:</span> 30% (add reference) |
|Yes | |Yes | ||
|No | |No | ||
|Yes | |Yes | ||
| − | |EXAMPLE | + | |<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). | ||
| Line 192: | Line 209: | ||
==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> | + | 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" | ||
| Line 202: | Line 219: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
7 | 7 | ||
| − | |EXAMPLE Loss | + | |<span class="blue-text">EXAMPLE:</span> Loss |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7:1- 159,335,973 [hg38] | chr7:1- 159,335,973 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7 | chr7 | ||
| Line 215: | Line 232: | ||
|Yes | |Yes | ||
|No | |No | ||
| − | |EXAMPLE | + | |<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 | + | |<span class="blue-text">EXAMPLE:</span> |
8 | 8 | ||
| − | |EXAMPLE Gain | + | |<span class="blue-text">EXAMPLE:</span> Gain |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8:1-145,138,636 [hg38] | chr8:1-145,138,636 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8 | chr8 | ||
| Line 232: | Line 249: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE | + | |<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). | ||
| Line 261: | Line 278: | ||
==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> | + | 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" | ||
| Line 271: | Line 288: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Co-deletion of 1p and 18q | Co-deletion of 1p and 18q | ||
| Line 277: | Line 294: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE: | + | |<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). | ||
| Line 289: | Line 306: | ||
==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 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 | + | 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" | ||
| Line 299: | Line 316: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE: TP53; Variable LOF mutations | + | |<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 | + | <span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations |
| − | |EXAMPLE: TSG | + | |<span class="blue-text">EXAMPLE:</span> TSG |
| − | |EXAMPLE: 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE: 30% (add Reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add Reference) |
| − | |EXAMPLE: IDH1 R123H | + | |<span class="blue-text">EXAMPLE:</span> IDH1 R123H |
| − | |EXAMPLE: EGFR amplification | + | |<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 /> | ||
|} | |} | ||
| Line 361: | Line 378: | ||
==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> | + | 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 |
|} | |} | ||
Latest revision as of 17:15, 6 September 2024
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Polycythemia Vera (PV).
(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)*
Gokce A. Toruner, MD, PhD
UT MD Anderson Cancer Center
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | Myeloid proliferations and neoplasms |
| Family | Myeloproliferative neoplasms |
| Type | Myeloproliferative neoplasms |
| Subtype(s) | Polycythaemia vera |
Definition / Description of Disease
- Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm (MPN).
- Increased red blood cell (RBC) production independent of normal regulation of erythropoiesis.
- Proliferation of other myeloid cells such as granulocytes and megakaryocytes are also frequently observed (panmyelosis).
- Very high majority of PV patients have JAK2 V617F or JAK2 exon 12 mutations.
- Phases of PV
- Polycythemic phase: Early phase characterized by increased hemoglobulin and hematocrit levels and increased RBC mass.
- Post polycythemic myelofibrosis: Later phase associated bone marrow fibrosis, ineffective hematopoiesis (and cytopenias) and extramedullary hematopoiesis.[1]
Synonyms / Terminology
- Polycythemia rubra vera
- Proliferative polycythemia
- Chronic erythema
- Maladie de Vaquez
Epidemiology / Prevalence
- Incidence rate: 1.8/100,000 in the US.
- Slight male predominance.
- Median age of diagnosis: 60 years, but it can occur any age.[2]
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 FeaturesThe content below was from the old template. Please incorporate above.
- Insidious onset of disease and PV is often discovered incidentally due to increased hemoglobin and hematocrit levels in a routine CBC
- Non-specific symptoms due to hypertension and vascular issues resulting from increased viscosity of the blood
- Frequent complaints: Headache, dizziness, vertigo, tinnitus, visual disturbances, pruritus, erythromelalgia
- Frequent physical examination findings: Splenomegaly, facial plethora
- About 20% of the cases have documented complications of arterial and venous thrombosis such as myocardial ischemia, cerebrovascular events, deep venous thrombosis, and hepatic portal vein thrombosis.
- May evolve into myelofibrosis, MDS or post PV blast phase (formerly known as acute leukemia)[1][3]
Sites of Involvement
- Bone marrow is the major affected site.
- Splenic and hepatic extramedullary hematopoiesis can be observed in later stages.
- Any organ can be damaged due to vascular involvement.[1]
Morphologic Features
Polycythemic phase
- Hypercellularity (notable in subcortical marrow space)
- Panmyelosis (with marked erythroid and megakaryocytic predominance)
- Pleomorphic megakaryocytes
- Decreased often absent iron deposits
Post polycythemic myelofibrosis phase
- Grade 2-3 BM fibrosis
- Decreased erythropoiesis (anemia) and granulopoiesis
- Manifestation of myeloid metaplasia and extramedullary hematopoiesis: Leukoeryhroblastosis, teardrop RBC, splenomegaly[1]
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:ImmunophenotypeThe content below was from the old template. Please incorporate above.No specific immunophenotypic characteristics
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.None
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)
Diagnosis[1]
- Major criteria
- Hemoglobin >16.5 g/dL in men or > 16 g/dL in women; or hematocrit >49% in men or > 48% in women or increased red blood cell mass
- Bone marrow tri-lineage proliferation with Pleomorphic mature megakaryocytes.
- Presence of JAK2 V617F mutation or JAK2 exon 12 mutations.
- Minor criterion:
· Subnormal serum erythropoietin level
For the diagnosis either all major criteria or first two major criteria and minor criterion should be fulfilled.
Prognosis[4]
- Adverse factors for leukemic transformation
- Advanced age
- Leukocytosis
- Abnormal karyotype (occur in progressive stages)
- AXL1, SRF2, IDH1, IDH2, RUNX1 mutations.
- Adverse prognostic factors for thrombosis
- Advanced age
- History of thrombosis
Therapeutic implications [5]
- Low risk (Age <60 years and no history of thrombosis)
- Phlebotomy to maintain hematocrit below 45%
- Low dose-aspirin
- High risk
- In addition to phlebotomy and aspirin, cytoreductive therapy (hydroxyurea of peginterferon alfa-2a.)
- For inadequate or loss of response with cytoreductive threapy: ruxolitinib or clinical trials
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. Do not delete table.)
| 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/LOHThe content below was from the old template. Please incorporate above.Frequent cytogenetic abnormalities are listed below[1].
Chromosome Number Gain/Loss/Amp/LOH Region 1 Gain 1q 8 Gain +8 9 Gain +9 20 Loss 20q
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 / PatternsThe content below was from the old template. Please incorporate above.Cytogenetic abnormalities is present about 20% of the cases (see genomic gain/loss/LOH section). Associated with progression and adverse prognosis[4][6].
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 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.)
| 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.
- JAK2 V617F mutations
- Highly frequent, but not diagnostic for PV, as more than half of Essential Throbocythemia and Primary Myelofibrosis have JAK2 V617F.
- This mutation is located in the pseudokinase domain of the JAK2 protein
- JAK2 exon 12 mutations
- Located in the so called linked region (amino acids 536- 547) between the SRC2 homology (SH2) and pseudokinase domains.
- Most of these mutations are in frame indels [7].
- Associated with younger age, increased hemoglobulin and hematocrit levels and lower WBC compated to cases with JAK2 V617F mutations [5]
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) JAK2 V617F Oncogene GOF; Driver 95-97% JAK2 Exon 12 mutations Oncogene GOF; Driver 3% Other Mutations
Most frequent mutations other than JAK2 in PV are TET2 and ASXL1 [8][9].
Type Gene/Region/Other Concomitant Mutations TET2, ASXL1, SH2B3, CEBPA, ZRSR2,S3FB1,CSF3R,KITSRSF2,IDH2,DNMT3A,SUZ12.SETB1,RUNX1.CBL,TP53,FLT3 [8][9]
Epigenomic Alterations
Methylation of promoter regions has not been documented, but mutations of genes important in epigenetic regulation are observed[8][9]
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete 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 InvolvedThe content below was from the old template. Please incorporate above.
- JAK2 is physically bound to homodimeric receptors: EPOR, MPL and G-CSFR and act as the catalytic part of these receptors upon the binding of the cytokine to the receptor.
- JAK2 V617F mutation results in non-cytokine dependent constitutive phosphorylation and activation of the down-stream STAT molecules and Pl3K and MAPK pathways[7].
Genetic Diagnostic Testing Methods
- Complete blood count
- Bone marrow aspiration and biopsy with trichrome reticulin stain
- NGS panels including JAK2 gene analysis
- Chromosome analysis and FISH
- Serum erythropoietin levels.
Familial Forms
- Geographical clustering in Pennsylvania [10] and Quebec [11]were observed
- JAK2 46/1 haplotype has been suggested for genetic predisposition[12]
- A whole exome study on a multi-generation family from Finland suggest several candidate SNPs[13]
- As of July 2020, a known family with an unequivocal high penetrance mutation has not been documented.
Additional Information
Put your text here
Links
Put your links here (use link icon at top of page)
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.)
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Thiele J, Kvasnicka HM, Orazi A, Tefferi A, Birgegard G, Barbui T (2017). Polycythemia Vera, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Editors. IARC Press: Lyon, France, p39-43
- ↑ Rm, Shallis; et al. (2020). "Epidemiology of the classical myeloproliferative neoplasms: The four corners of an expansive and complex map". PMID 32517877 Check
|pmid=value (help). - ↑ Tefferi A. Clinical manifestations and diagnosis of polycythemia vera https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-polycythemia-vera (last accessed 8/1/2020)
- ↑ 4.0 4.1 A, Tefferi; et al. (2019). "Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management". PMID 30281843.
- ↑ 5.0 5.1 NCCN guidelines for myefoloproliferative neoplasms https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf (last accessed 8/1/2020)
- ↑ G, Tang; et al. (2017). "Characteristics and clinical significance of cytogenetic abnormalities in polycythemia vera". doi:10.3324/haematol.2017.165795. PMC 5685217. PMID 28473622.CS1 maint: PMC format (link)
- ↑ 7.0 7.1 W, Vainchenker; et al. (2017). "Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms". PMID 28028029.
- ↑ 8.0 8.1 8.2 A, Tefferi; et al. (2016). "Targeted deep sequencing in polycythemia vera and essential thrombocythemia". doi:10.1182/bloodadvances.2016000216. PMC 5744051. PMID 29296692.CS1 maint: PMC format (link)
- ↑ 9.0 9.1 9.2 A, Tefferi; et al. (2020). "Mutation-enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera". PMID 31945802.
- ↑ V, Seaman; et al. (2009). "Use of molecular testing to identify a cluster of patients with polycythemia vera in eastern Pennsylvania". PMID 19190168.
- ↑ M, Le; et al. (2019). "Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada". PMID 31381139.
- ↑ D, Olcaydu; et al. (2009). "A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms". PMID 19287385.
- ↑ Eam, Hirvonen; et al. (2017). "Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera". doi:10.1186/s40246-017-0102-x. PMC 5397753. PMID 28427458.CS1 maint: PMC format (link)
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: “Polycythaemia vera”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Polycythaemia_vera.