Dual-Driver Myeloproliferative Neoplasm: Concurrent p190CML andV617F Mutation: A Case Report and Literature Review.
Key claim: In a rare dual-driver MPN with concurrent JAK2 V617F and isolated p190 (e1a2) BCR-ABL1, high-sensitivity RT-PCR plus integrated morphology enabled correct diagnosis and TKI therapy that reduced the BCR-ABL1/ABL1 ratio from 88.5% to 0.79%.
Abstract
The concurrent occurrence ofrearrangement andV617F 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, asdefines Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), whileV617F characterizes Ph-negative MPNs. We report a male patient in his 50s with a previously detectedV617F 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 knownV617F mutation, prompted targeted molecular investigation. High-sensitivity RT-PCR confirmed an isolated e1a2 (p190)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 concurrentV617F 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/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 concurrenttesting, is essential for accurate diagnosis, prognostication, and therapy selection in these rare dual-driver cases.
Why this matters
In a rare dual-driver MPN with concurrent JAK2 V617F and isolated p190 (e1a2) BCR-ABL1, high-sensitivity RT-PCR plus integrated morphology enabled correct diagnosis and TKI therapy that reduced the BCR-ABL1/ABL1 ratio from 88.5% to 0.79%.