Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement

Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement is a rare hematologic malignancy characterized by chromosomal translocations involving the platelet-derived growth factor receptor beta (PDGFRB) gene located on chromosome 5q32. This condition was previously classified under chronic eosinophilic leukemia or atypical chronic myeloproliferative disorders. The rearrangement results in a constitutively active tyrosine kinase fusion protein that drives uncontrolled proliferation of myeloid and sometimes lymphoid cells. The most common translocation partner is ETV6 (TEL), resulting in the t(5;12)(q32;p13) fusion, though over 30 different partner genes have been identified. The disease primarily affects the hematopoietic (blood-forming) system and commonly presents with features of chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, or other myeloproliferative neoplasms. Key clinical features include prominent eosinophilia, splenomegaly (enlarged spleen), hepatomegaly, and elevated white blood cell counts. Patients may experience fatigue, weight loss, night sweats, and symptoms related to organ infiltration by eosinophils, including skin rashes, pulmonary symptoms, and cardiac complications such as endomyocardial fibrosis. Some patients may present with lymphoblastic lymphoma, particularly T-cell lymphoblastic lymphoma, either alone or concurrent with a myeloproliferative neoplasm. The treatment landscape for this condition has been transformed by the introduction of imatinib, a tyrosine kinase inhibitor. PDGFRB-rearranged neoplasms are exquisitely sensitive to imatinib, often at lower doses than those used for BCR-ABL1-positive chronic myeloid leukemia. Most patients achieve complete hematologic and cytogenetic remission with imatinib therapy. This remarkable treatment response makes accurate diagnosis critical, as it directly impacts therapeutic decisions and prognosis. Without treatment, the disease may progress to acute leukemia. Allogeneic hematopoietic stem cell transplantation may be considered in cases of imatinib resistance or disease transformation.

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