A Review of Clonal Relationships in Myeloproliferative Neoplasms With Co-Mutations of JAK2, CALR or MPL and BCR::ABL1

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 25; no. 4; pp. 249 - 253
• Main Authors: Noorafrooz, Mohammadamin, Ghods, Sanaz, Gale, Robert Peter, Noorafrooz, Ramin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2025
• Subjects: Branching evolution; Calreticulin - genetics; Clonal Evolution; Clonal interactions; CML; Fusion Proteins, bcr-abl - genetics; Humans; Janus Kinase 2 - genetics; MPNs; Mutation; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - pathology; Proto-Oncogene Proteins c-abl - genetics; Proto-Oncogene Proteins c-bcr - genetics; Receptors, Thrombopoietin - genetics; Tyrosine kinase inhibitors; CML; Branching evolution; MPNs; Clonal interactions; Tyrosine kinase inhibitors
• ISSN: 2152-2650; 2152-2669; 2152-2669
• DOI: 10.1016/j.clml.2024.11.007

BCR::ABL1-negative myelo-proliferative neoplasms (MPNs) are characterized by mutations in JAK2, CALR, or MPL. Usually these mutations are co-exclusive of each other and of BCR::ABL1. We reviewed clonal interactions in 177 subjects with mutations in JAK2, CALR, or MPL and BCR::ABL1 including JAK2/BCR::ABL1 (N = 142), CALR/BCR::ABL1 (N = 31), MPL/BCR::ABL1 (N = 3). Co-mutations can arise in the same clone or in different sub-clones. In this review we used clonality data, mutation sequencing and therapy response evaluation to address this question. We found that in subjects with JAK2/BCR::ABL1 co-mutations there is a complex, branched clonal evolution. In contrast, in subjects with CALR/BCR::ABL1, co-mutations are in different sub-clones. There are too few data in subjects with MPL/BCR::ABL1 to critically analyze. However, indirect methods for assessing clonality limit our conclusions. Understanding clonal architecture of MPNs with co-mutations is needed to understand the underlying biology and give appropriate therapy.