Difference between revisions of "HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement"
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| − | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11- | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement]]. |
}}</blockquote> | }}</blockquote> | ||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
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__TOC__ | __TOC__ | ||
| − | ==Cancer Category/Type== | + | ==Cancer Category / Type== |
Myeloid Neoplasms/Acute myeloid leukemia | Myeloid Neoplasms/Acute myeloid leukemia | ||
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</blockquote> | </blockquote> | ||
| − | ==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.'') </span> | ||
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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)== | + | ==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 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> | ||
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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. | ||
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| + | <blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}} | ||
| + | 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>. | ||
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| + | </blockquote> | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
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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. | ||
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<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>. | ||
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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]] | [[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]] | ||
Revision as of 15:36, 30 November 2023
Haematolymphoid Tumours (5th ed.)
 | This page is under construction |
editHAEM5 Conversion NotesThis page was converted to the new template on 2023-11-30. The original page can be found at HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement.
Primary Author(s)*
Christopher Sullivan, MD, MPH and Daynna J. Wolff, PhD
Cancer Category / Type
Myeloid Neoplasms/Acute myeloid leukemia
Cancer Sub-Classification / Subtype
Myeloid/Lymphoid Neoplasms 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)
| 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 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)
| 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.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
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)
| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE
7 |
EXAMPLE Loss | EXAMPLE
chr7:1- 159,335,973 [hg38] |
EXAMPLE
chr7 |
Yes | Yes | No | EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE
8 |
EXAMPLE Gain | EXAMPLE
chr8:1-145,138,636 [hg38] |
EXAMPLE
chr8 |
No | No | No | EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference). |
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| EXAMPLE
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.
Gene Mutations (SNV / INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.)
| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.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
Put your text here
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.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
Put your text here
Links
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 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.
- ↑ 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.
- ↑ 3.0 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.
- ↑ 4.0 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.
- ↑ 5.0 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
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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 11/30/2023, https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRB_rearrangement.