Myeloid/lymphoid neoplasms associated with eosinophilia and abnormality of PDGFRA, PDGFRB, FGFR1 or JAK2

Myeloid/lymphoid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, FGFR1, or JAK2 are a group of rare blood cancers classified by the World Health Organization (WHO) as a distinct category of hematologic malignancies. These disorders are characterized by the abnormal overproduction of eosinophils (a type of white blood cell) along with specific chromosomal rearrangements involving one of four tyrosine kinase genes: PDGFRA (platelet-derived growth factor receptor alpha), PDGFRB (platelet-derived growth factor receptor beta), FGFR1 (fibroblast growth factor receptor 1), or JAK2 (Janus kinase 2). These genetic rearrangements lead to constitutively activated fusion proteins that drive uncontrolled cell growth in the bone marrow and blood. The diseases primarily affect the hematopoietic (blood-forming) system, but organ damage from eosinophilic infiltration can involve the heart (endomyocardial fibrosis, restrictive cardiomyopathy), lungs (pulmonary infiltrates, fibrosis), skin (rashes, urticaria, angioedema), gastrointestinal tract, and nervous system. Patients may present with marked eosinophilia, splenomegaly, hepatomegaly, lymphadenopathy, fatigue, and constitutional symptoms such as fever and weight loss. Depending on the specific genetic abnormality, the disease may manifest as chronic eosinophilic leukemia, myeloproliferative neoplasm, myelodysplastic syndrome, or acute leukemia (myeloid or lymphoblastic). Treatment varies significantly based on the underlying genetic abnormality. PDGFRA-rearranged neoplasms (most commonly the FIP1L1-PDGFRA fusion) are highly sensitive to imatinib, a tyrosine kinase inhibitor, often achieving complete and durable remissions at low doses. PDGFRB-rearranged neoplasms also respond well to imatinib. In contrast, FGFR1-rearranged neoplasms (also known as 8p11 myeloproliferative syndrome) are typically aggressive, often progressing to acute leukemia, and generally require intensive chemotherapy and allogeneic hematopoietic stem cell transplantation, though newer FGFR inhibitors such as pemigatinib have shown promise. JAK2-rearranged neoplasms may respond to JAK inhibitors such as ruxolitinib, though evidence is more limited. Early diagnosis through cytogenetic and molecular testing is critical for guiding appropriate targeted therapy.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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