Minor‑Breakpoint (p190) BCR‑ABL1 Chronic Myeloid Leukemia Nineteen Years After JAK2‑Mutant Polycythemia Vera: A Unique Evolutionary Case Report

JAK2 V617F‑mutant polycythemia vera (PV) and BCR‑ABL1‑positive chronic myeloid leukemia (CML) are traditionally considered mutually exclusive myeloproliferative neoplasms. Although a few reports describe sequential acquisition of both drivers, the emergence of the minor‑breakpoint p190 (e1a2) BCR‑ABL1 transcript in a long‑standing PV background remains extremely rare.

A 69‑year‑old man with JAK2 V617F‑positive PV, diagnosed in 2006 and managed with phlebotomy and hydroxyurea, developed progressive splenomegaly. Ruxolitinib 10 mg twice daily was initiated in May 2023. In early 2025, surveillance PCR unexpectedly detected BCR‑ABL1 p190 7.3 % (International Scale [IS]), rising to 8.5 % one month later; the p210 transcript was undetectable. Bone‑marrow biopsy confirmed chronic‑phase CML (65 % cellularity, MF‑2 myelofibrosis, 1 % blasts) with t(9;22), del(5q), and pathogenic variants in ASXL1, DNMT3A, U2AF1, and CHEK2. Ruxolitinib was continued, and dasatinib 50 mg once daily was initiated, achieving a complete hematologic response by week 4; three‑month molecular assessment is pending.

This case illustrates a rare transformation of PV to p190 BCR‑ABL1 CML nearly two decades after the initial JAK2 mutation. Long‑term JAK inhibition, coupled with accumulating epigenetic and cytogenetic lesions, may have reshaped the marrow niche and allowed expansion of a dormant, highly active p190 subclone—highlighting remarkable clonal plasticity at the interface of JAK‑STAT and ABL signaling. The early, well‑tolerated hematologic remission achieved with concurrent dasatinib and ruxolitinib supports dual‑pathway inhibition as a mechanistically sound strategy that could both suppress residual JAK2‑mutant cells and facilitate molecular eradication of p190 CML. Systematic data collection and prospective studies are needed to determine whether this approach can benefit other patients who traverse the classical boundary between Philadelphia‑negative and Philadelphia‑positive myeloproliferative neoplasms.