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WHO Classification of Tumours
Myeloid neoplasms with PDGFRB rearrangement
Tumours of haematopoietic and lymphoid tissues


Definition

A distinctive type of myeloid neoplasm occurs in association with rearrangement of PDGFRB at 5q31~33 (Table 3.02). Usually there is t(5;12)(q31~33;p12) with formation of an ETV6-PDGFRB fusion gene
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Golub TR, Barker GF, Lovett M, Gilliland DG (1994)
Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.
Cell 77: 307-16




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Keene P, Mendelow B, Pinto MR, Bezwoda W, MacDougall L, Falkson G, Ruff P, Bernstein R (1987)
Abnormalities of chromosome 12p13 and malignant proliferation of eosinophils: a nonrandom association.
Br J Haematol 67: 25-31



. In uncommon variants, other translocations with a 5q31~33 breakpoint lead to the formation of other fusion genes, also incorporating part of PDGFRB (Table 3.03). In cases with t(5;12), and in the variant translocations, there is synthesis of an aberrant, constitutively activated tyrosine kinase. The haematological features are most often those of chronic myelomonocytic leukaemia (CMML) (usually with eosino­philia) but some patients have been characterized as atypical chronic myeloid leukaemia, BCR-ABL1 negative (aCML) (usually with eosino­philia), CEL and MPN with eosino­philia
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Bain BJ, Fletcher SH (2007)
Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome.
Immunol Allergy Clin North Am 27: 377-88




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Steer EJ, Cross NC (2002)
Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta.
Acta Haematol 107: 113-22



; single cases have been reported of AML, probably superimposed on primary myelofibrosis
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Tokita K, Maki K, Tadokoro J, Nakamura Y, Arai Y, Sasaki K, Eguchi-Ishimae M, Eguchi M, Mitani K (2007)
Chronic idiopathic myelofibrosis expressing a novel type of TEL-PDGFRB chimaera responded to imatinib mesylate therapy.
Leukemia 21: 190-2



, and of juvenile myelomonocytic leukaemia (JMML)
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Morerio C, Acquila M, Rosanda C, Rapella A, Dufour C, Locatelli F, Maserati E, Pasquali F, Panarello C (2004)
HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2).
Cancer Res 64: 2649-51



, the latter associated with a variant fusion gene. Eosinophilia is usual but not invariable
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Steer EJ, Cross NC (2002)
Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta.
Acta Haematol 107: 113-22



. Acute transformation can occur, often in a relatively short period of time. MPN with PDGFRB rearrangement is sensitive to ­tyrosine kinase inhibitors such as imatinib
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Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM (2002)
Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.
N Engl J Med 347: 481-7



.

> Variants
A number of molecular variants of MPN with ETV6-PDGFRB fusion have been reported

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Bain BJ, Fletcher SH (2007)
Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome.
Immunol Allergy Clin North Am 27: 377-88




Click to access Pubmed
Steer EJ, Cross NC (2002)
Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta.
Acta Haematol 107: 113-22



. In addition, a patient who acquired eosinophilia at relapse of AML was found to have acquired t(5;14) (q33;q22) with a TRIP11-PDGFRB fusion gene. A number of other patients have rearrangement of PDGFRB but with the second gene involved being unknown. Complex rearrangements appear to be common (e.g. a small inversion as well as translocation)
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Steer EJ, Cross NC (2002)
Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta.
Acta Haematol 107: 113-22



. Because of the therapeutic implications, FISH (break-apart FISH with a PDGFRB probe) is indicated in all patients with a presumptive diagnosis of MPN who have a 5q31~33 breakpoint, particularly, but not only, if there is eosinophilia. However, FISH analysis does not always demonstrate rearrangement of PDGFRB, even when it is detectable on Southern Blot analysis
Click to access Pubmed
Steer EJ, Cross NC (2002)
Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta.
Acta Haematol 107: 113-22



. Molecular analysis is not indicated if there is no 5q31~33 breakpoint on classical cyto­genetic analysis since all cases reported to date have had a cytogenetically detectable abnormality.

> Related Topics
Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1
Chronic eosinophilic leukaemia, NOS
Introduction: Myeloid Neoplasms