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- W3196992014 abstract "Concomitant BCR-ABL1 and JAK2V617F in myeloproliferative neoplasms (MPNs) is rare, and its pathogenesis and clinical significance are unclear.To investigate the clonal relationship between the 2 genomic alterations, as well as the clinicopathologic impact.Retrospective analysis of MPNs with sequential development of BCR-ABL1 and JAK2V617F.Of 6 cases, 5 had JAK2V617F-positive MPN diagnosed before acquiring BCR-ABL1 years later, and 1 had BCR-ABL1+ chronic myeloid leukemia before JAK2V617F-positive myelofibrosis completely replaced the BCR-ABL1+ clone 1 year after tyrosine kinase inhibitor therapy. Among the former group, treatment for the initial MPN involved hydroxyurea, ruxolitinib, and/or supportive care, and the latency to the development of JAK2V617F ranged from 4 to 13 years (median of 9 years). Four cases showed retention of JAK2V617F, whereas BCR-ABL1 emerged as the major clone, including 2 cases that exhibited parallel increases in JAK2V617F and BCR-ABL1 burdens, with both genomic markers exceeding 50%. Three patients received stem cell transplants and demonstrated sustained engraftment, with the genomic markers below detectable levels.Most MPNs with concomitant JAK2V617F and BCR-ABL1 are actually composite MPNs with a second hit residing on a different clone. Rare cases demonstrate a subclone harboring a double-hit in a background of a JAK2V617F-positive stem line clone. The probability of a double-hit with a BCR-ABL1+ stem line clone is probably reduced by effective tyrosine kinase inhibitor treatment. The treatment often involves combined kinase inhibitors and/or hydroxyurea, but the outcome is unpredictable; hematopoietic stem cell transplantation may be the ultimate therapeutic option for this complicated disease." @default.
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- W3196992014 date "2021-09-10" @default.
- W3196992014 modified "2023-10-15" @default.
- W3196992014 title "Sequential Development of JAK2V617F Mutation and BCR-ABL1 Fusion in Individual Patients With Myeloproliferative Neoplasms: A Linear Clonal Evolution or Parallel Clonal Competition?" @default.
- W3196992014 doi "https://doi.org/10.5858/arpa.2021-0096-oa" @default.
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