Difference between revisions of "HAEM5:Myeloid/lymphoid neoplasm with JAK2 rearrangement"
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{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with JAK2 rearrangement}} | {{DISPLAYTITLE:Myeloid/lymphoid neoplasm with JAK2 rearrangement}} | ||
| − | [[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:Myeloid/Lymphoid Neoplasms with PCM1-JAK2]]. |
}}</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 12: | Line 15: | ||
__TOC__ | __TOC__ | ||
| − | == | + | ==WHO Classification of Disease== |
| − | + | {| class="wikitable" | |
| − | + | !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 JAK2 rearrangement | ||
| + | |} | ||
==Definition / Description of Disease== | ==Definition / Description of Disease== | ||
| Line 43: | Line 60: | ||
==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 78: | Line 95: | ||
==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 84: | Line 101: | ||
!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 111: | Line 128: | ||
!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 147: | Line 164: | ||
==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 157: | Line 174: | ||
!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 170: | Line 187: | ||
|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 187: | Line 204: | ||
|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 198: | Line 215: | ||
==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 208: | Line 225: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Co-deletion of 1p and 18q | Co-deletion of 1p and 18q | ||
| Line 214: | Line 231: | ||
|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 226: | Line 243: | ||
==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 236: | Line 253: | ||
!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 269: | Line 286: | ||
==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 17:21, 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:Myeloid/Lymphoid Neoplasms with PCM1-JAK2.
(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)*
Jessica Snider, M.D. 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 JAK2 rearrangement |
Definition / Description of Disease
A hematologic neoplasm comprised of pluripotent (lymphoid-myeloid) stem cells characteristically seen with eosinophilia that result from the formation of a fusion between the PCM1 and JAK2 genes, leading to the expression of an aberrant tyrosine kinase. Due to its pluripotent nature, the hematologic stem cells can give rise to eosinophils, neutrophils, B-lymphoid and T-lymphoid cells. The presence of eosinophilia is not required for the diagnosis.[1][2][3]
Synonyms / Terminology
Chronic eosinophilic leukemia with PCM1/JAK2
PCM1/JAK2 –associated chronic eosinophilic leukemia
Myeloid and lymphoid neoplasms associated with JAK2 rearrangement
JAK2-associated Hypereosinophilic syndrome
Myeloid and lymphoid neoplasms with JAK2 rearrangement
Myeloproliferative variant of the hypereosinophilic syndrome
Epidemiology / Prevalence
This disease is rare; the incidence of hypereosinophilia in general is only 0.036 per 100,000 and genetic causes represent only a small portion of these[4]There is a significant male predominance with a median age of 47 years old (age range 7-77)[1] As of August 2018, only 40 cases had been reported[5]
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.Patients typically present with features of a myeloproliferative disorder or MDS/MPN and most have eosinophilia and/or bone marrow fibrosis[5][6]. Patients in chronic phase tend to progress to AML quickly; some present with de novo acute leukemia, either myeloid or lymphoid[6][5]
In general, patients with this disorder have weakness/fatigue (~26%), cough (~24%), myaligias/angioedema (~14%), rash or fever (~12%) and rhinitis (~10%)[7] ; lymphadenopathy and splenomegaly are common[5]
Sites of Involvement
Peripheral blood and bone marrow
Morphologic Features
Patients often have a hypercellular bone marrow with increased eosinophils and fibrosis[1][5].Increased granuolpoiesis with eosinophilia and neutrophil precursors, including myeloblasts[1][5]. Dyserythropoiesis and dysgranulopoiesis are not typical but may be observed[1][5] Increased lymphoblasts may also be seen with blast cells having high nuclear to cytoplasmic ratios and open chromatin. If eosinophilia is present, it is comprised mainly of mature eosinophils with scattered immature forms. Eosinophilic abnormalities can be seen and include sparse granulation with small forms, vacuoles in the cytoplasm, increased eosinophil size, and nuclear hypo- and hypersegmentation.
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.IHC can be used to characterize acute myeloid transformation and myeloblasts express dim CD45, dim CD34, dim CD117, HLA-DR, dim CD33, and dim CD13[1]. In addition, For the cases with lymphoid components, IHC can assist with assessment and show dim CD19 and dim CD10, consistent with lymphoblast lineage[1][5].
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.
Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence t(8;9)(p22;p24.1) 3'JAK2 / 5'PCM1 der(8) rare
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)
Most patients present with MPN with variable degrees of eosinophilia in blood and/or bone marrow, frequent marrow fibrosis, and large aggregates of immature erythroid precursors, and clinically exhibit hepatosplenomegagly and lymphadenopathy[5]. However, diagnosis may be difficult in cases without obvious eosinophilia.
Due to the variations in presentation, the prognosis is mainly dependent on the phase at presentation, but generally tends to have an aggressive course1. There currently are no approved therapies for PCM1/JAK2-mediated myeloid/lymphoid neoplasm with eosinophilia; however, JAK2 inhibitors have been approved for other hematopoietic neoplasms with constitutively activated JAK2 kinases.2
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.There are no known recurrent genomic loss/gain or LOH pattern associated with entity.
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.There are no known secondary chromosomal changes and no pattern of other chromosome aberrations.
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.Given the rarity of the entity, there are no known recurrent aberrations. For the largest series studied, most cases were negative for mutations. However, some cases showed variants in genes associated with myeloid malignancies (ASXL1, RUNX1, SRSF2, TET2, BCOR) and one patient with B-ALL transformation showed variants in ETV6 and TP53[5]
Other Mutations
Epigenomic Alterations
There are no known epigenomic modifiers.
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.PCM1 (pericentriolar material 1) is a protein present in cytoplasmic granules and can be found in association with the centrosome. PCM1 is indirectly responsible for microtubule anchoring, which is necessary for a variety of cellular functions, including intracellular transport and cell division. The gene is located at band 8p22 and includes 41 exons.5
JAK2 (janus kinase 2) is a tyrosine kinase responsible for activation of the JAK-STAT pathway by mediating tyrosine phosphorylation, leading to cell proliferation and differentiation. Constitutive activation of JAK2 can result from chromosomal translocations and lead to uncontrolled proliferation of hematopoietic cells. The gene is located at band 9p24.1 and includes 25 exons.6
The PCM1-JAK2 fusion product retains the coiled-coil domains of PCM1 and the activating tyrosine kinase domain of JAK2. Thus PCM1-JAK2 fusion produces an aberrant tyrosine kinase that results in constitutive activation of the JAK2–STAT pathway[6]
Genetic Diagnostic Testing Methods
Diagnosis of this entity is made when a chromosome analysis showing a t(8;9) correlates with the clinical and morphological phenotype of the patient and/or when the fusion is confirmed by ancillary testing. FISH with a dual color, dual fusion probe for PCM1-JAK2 and sequencing of RNA to detect the functional fusion are the most commonly used methods to confirm this diagnosis. FISH with a JAK2 break-apart probe may also provide useful information to confirm a diagnosis.
However, because the clinical presentation can vary and this disease can show many overlapping morphological features of other entities, the PCM1-JAK2 fusion or 8;9 translocation may be detected without overt suspicion. Therefore, agnostic genomic methods such as large panels of RNA fusions known to be associated with myeloid or lymphoid malignancies, whole exome/genome sequencing and occasionally chromosomal microarray analysis may provide evidence for this diagnosis.
Familial Forms
No familial forms have been documented.
Additional Information
Links
References
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- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Bain BJ, Horny HP, Arber DA, et al. Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2., 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, p129-171.
- ↑ Reiter, Andreas; et al. (2017). "Myeloid neoplasms with eosinophilia". Blood. 129 (6): 704–714. doi:10.1182/blood-2016-10-695973. ISSN 0006-4971.
- ↑ Baer, Constance; et al. (2018). "Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2". Haematologica. 103 (8): e348–e350. doi:10.3324/haematol.2017.187302. ISSN 0390-6078. PMC 6068021. PMID 29567772.CS1 maint: PMC format (link)
- ↑ Crane, Martin M.; et al. (2010). "Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence". Journal of Allergy and Clinical Immunology. 126 (1): 179–181. doi:10.1016/j.jaci.2010.03.035. PMC 5781228. PMID 20639012.CS1 maint: PMC format (link)
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 Tang, Guilin; et al. (2019). "Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study". Modern Pathology. 32 (4): 490–498. doi:10.1038/s41379-018-0165-9. ISSN 0893-3952.
- ↑ 6.0 6.1 6.2 Hoeller, Sylvia; et al. (2011). "PCM1–JAK2-fusion: a potential treatment target in myelodysplastic–myeloproliferative and other hemato-lymphoid neoplasms". Expert Opinion on Therapeutic Targets. 15 (1): 53–62. doi:10.1517/14728222.2011.538683. ISSN 1472-8222.
- ↑ Gotlib, Jason (2017). "World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management". American Journal of Hematology. 92 (11): 1243–1259. doi:10.1002/ajh.24880.
Notes
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