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

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.