Alternative titles; symbols
ORPHA: 86830; DO: 0111344;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q32 | Myeloproliferative disorder with eosinophilia | 131440 | Autosomal dominant | 4 | PDGFRB | 173410 |
A number sign (#) is used with this entry because in many instances chronic myeloproliferative disorder with eosinophilia is caused by a translocation between chromosomes 12 and 5, creating an ETV6 (600618)-PDGFRB (173410) fusion gene.
Keene et al. (1987) suggested a causal relationship between abnormality of the 12p13 band and malignant eosinophil proliferation; 2 of the 4 patients in their report had translocations involving chromosome 5q3. Golub et al. (1994) showed that the previously described t(5;12) translocation, characteristic of some cases of chronic myelomonocytic leukemia, was associated with a fusion gene linking ETV6 with platelet-derived growth factor receptor-beta (PDGFRB), which maps to 5q31-q32. A considerable number of cases of chronic myeloproliferative disorder associated with a t(5;12) translocation have been reported, and the PDGFRB gene is known to be rearranged in some of these cases. There are additional cases involving translocations of the PDGFRB-containing region of chromosome 5 and chromosome partners other than 12p13, e.g., chromosome 14 (see 604505). Although heterogeneous, all these leukemias have some common features, most notably the frequent presence of eosinophilia in peripheral blood and bone marrow.
Apperley et al. (2002) reported treatment of 4 patients who had chronic myeloproliferative disorders and chromosome translocations involving 5q33. Three of the 4 patients presented with leukocytosis and eosinophilia; their leukemia cells carried the ETV6/PDGFRB fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB on chromosome 5 and an unknown partner gene; he also had extensive raised, ulcerated skin lesions that had been present for a long time. All 4 patients responded to treatment with imatinib mesylate, an inhibitor of the kinase activity of PDGFRB and other protein tyrosine kinases.
Apperley, J. F., Gardembas, M., Melo, J. V., Russell-Jones, R., Bain, B. J., Baxter, E. J., Chase, A., Chessells, J. M., Colombat, M., Dearden, C. E., Dimitrijevic, S., Mahon, F.-X., Marin, D., Nikolova, Z., Olavarria, E., Silberman, S., Schultheis, B., Cross, N. C. P., Goldman, J. M. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. New Eng. J. Med. 347: 481-487, 2002. [PubMed: 12181402] [Full Text: https://doi.org/10.1056/NEJMoa020150]
Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77: 307-316, 1994. [PubMed: 8168137] [Full Text: https://doi.org/10.1016/0092-8674(94)90322-0]
Keene, P., Mendelow, B., Pinto, M. R., Bezwoda, W., MacDougall, L., Falkson, G., Ruff, P., Bernstein, R. Abnormalities of chromosome 12p13 and malignant proliferation of eosinophils: a nonrandom association. Brit. J. Haemat. 67: 25-31, 1987. [PubMed: 3478077] [Full Text: https://doi.org/10.1111/j.1365-2141.1987.tb02291.x]