Targeted Therapy for a Rare PDGFRB-Rearranged Myeloproliferative Neoplasm: A Case Report

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases originating from hematopoietic stem cell transformation, characterized by clonal proliferation of hematopoietic progenitors. A specific subset includes myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions, particularly involving PDGFR A or B, which are sensitive to TK inhibitor treatment. We report a case of a 21-year-old patient with a myeloproliferative/ myelodysplastic neoplasm, presenting with hyperleukocytosis, anemia, thrombocytopenia, and elevated LDH. Peripheral blood smear showed hypogranular neutrophils, eosinophils, basophils, and myeloid precur-sors. Absence of BCR::ABL1 and mutations in JAK2, CALR, and MPL ex-cluded common MPNs. Cytogenetic analysis revealed a rearrangement between chromosomes 5 and 14. FISH analysis confirmed an inverted insertion from chromosome 5 to chromosome 14, involving the PDGFRB gene. WGS and RNAseq identified a fusion between PDGFRB and CCDC88C, causing constitutive activation of PDGFRB. The fusion gene was confirmed by sequencing. This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case demonstrates how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, resulting in effective treatment and molecular remission.