Dual-Driver Myeloproliferative Neoplasm: Concurrent p190 BCR::ABL1 CML and JAK2 V617F Mutation: A Case Report and...

The concurrent occurrence of BCR::ABL1 rearrangement and JAK2 V617F mutation is an exceptionally rare phenomenon, with reported frequencies of 0.2%-2.5% in tested myeloproliferative neoplasm (MPN) cohorts and an estimated overall rate of approximately 0.4% in patients screened for both alterations. These molecular drivers are generally considered mutually exclusive, as BCR::ABL1 defines Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), while JAK2 V617F characterizes Ph-negative MPNs. We report a male patient in his 50s with a previously detected JAK2 V617F mutation, initially managed as essential thrombocythemia, who later presented with leukocytosis, macrocytic anemia, thrombocytopenia, and absolute monocytosis. Bone marrow demonstrated marked myeloid hyperplasia with atypical megakaryocytes, comprising scattered dwarf forms together with larger forms with "cloud-like" nuclei and focal reticulin fibrosis (MF-1). These findings, together with the known JAK2 V617F mutation, prompted targeted molecular investigation. High-sensitivity RT-PCR confirmed an isolated e1a2 (p190) BCR::ABL1 transcript, the minor breakpoint cluster region isoform occurring in only 1%-2% of CML cases, with the complete absence of the p210 isoform, alongside a concurrent JAK2 V617F mutation (allele burden 16%). Standard p210-focused quantitative assays would have produced a false-negative result in this case. The patient received first-line asciminib and was subsequently transitioned to dasatinib, with the BCR::ABL1/ABL1 ratio declining from 88.5% at diagnosis to 0.79% at most recent assessment. This case highlights the critical importance of integrated morphologic, cytogenetic, and molecular evaluation in atypical MPN presentations. The admixed megakaryocytic atypia superimposed on myeloid hyperplasia reflected the coexistence of two drivers. Comprehensive profiling, including high-sensitivity RT-PCR capable of detecting the p190 isoform and concurrent JAK2 testing, is essential for accurate diagnosis, prognostication, and therapy selection in these rare dual-driver cases.