Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement

Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement (also known as myeloid/lymphoid neoplasm with PDGFRA rearrangement, or previously classified under chronic eosinophilic leukemia associated with FIP1L1-PDGFRA) is a rare hematologic malignancy characterized by the abnormal rearrangement of the PDGFRA gene (platelet-derived growth factor receptor alpha), most commonly through a cryptic interstitial deletion on chromosome 4q12 that creates the FIP1L1-PDGFRA fusion gene. This fusion produces a constitutively active tyrosine kinase that drives uncontrolled proliferation of myeloid and sometimes lymphoid cells. The disease predominantly affects the blood and bone marrow, but can also involve the spleen, lymph nodes, and other organs. It most commonly presents with marked eosinophilia (elevated eosinophil counts), and the resulting tissue infiltration by eosinophils can cause significant damage to the heart (endomyocardial fibrosis, restrictive cardiomyopathy), lungs (pulmonary infiltrates, fibrosis), skin (rashes, pruritus), and gastrointestinal tract. Patients may present with fatigue, cough, dyspnea, skin lesions, and splenomegaly. In some cases, the disease manifests as acute myeloid leukemia or T-lymphoblastic lymphoma rather than chronic eosinophilic leukemia. This condition occurs predominantly in males, with a striking male-to-female ratio. The disease is classified by the World Health Organization (WHO) as a distinct entity within the category of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions. A hallmark of this disease is its remarkable sensitivity to imatinib, a tyrosine kinase inhibitor. Treatment with low-dose imatinib (typically 100 mg daily) produces rapid and durable complete hematologic and molecular remissions in the vast majority of patients, making it the first-line therapy. This targeted treatment has dramatically improved outcomes, transforming what was previously a life-threatening condition into a manageable disease. For the rare cases with resistance to imatinib (often due to a T674I mutation in PDGFRA), second-generation tyrosine kinase inhibitors or allogeneic stem cell transplantation may be considered.

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