Sequential Development of JAK2V617F Mutation and BCR-ABL1 Fusion in Individual Patients With Myeloproliferative Neoplasms.

Journal Article (Journal Article)

CONTEXT.—: Concomitant BCR-ABL1 and JAK2V617F in myeloproliferative neoplasms (MPNs) is rare, and its pathogenesis and clinical significance are unclear. OBJECTIVE.—: To investigate the clonal relationship between the 2 genomic alterations, as well as the clinicopathologic impact. DESIGN.—: Retrospective analysis of MPNs with sequential development of BCR-ABL1 and JAK2V617F. RESULTS.—: 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. CONCLUSIONS.—: 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.

Full Text

Duke Authors

Cited Authors

  • Zhao, Y; Reddi, D; McCracken, J; Iranzad, N; Rehder, C; Neff, J; Wang, E

Published Date

  • June 1, 2022

Published In

Volume / Issue

  • 146 / 6

Start / End Page

  • 710 - 717

PubMed ID

  • 34506622

Electronic International Standard Serial Number (EISSN)

  • 1543-2165

Digital Object Identifier (DOI)

  • 10.5858/arpa.2021-0096-OA

Language

  • eng

Conference Location

  • United States