Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1 -Negative Myeloproliferative Neoplasms.

BCR::ABL1 -negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations are acquired in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells in peripheral blood and fibrosis in bone marrow. Mutations in JAK2 , MPL , and CALR are frequently found in BCR::ABL1 -negative MPNs, and detecting typical mutations in these three genes has become essential for the diagnosis of BCR::ABL1 -negative MPNs. Furthermore, comprehensive gene mutation and expression analyses performed using massively parallel sequencing have identified gene mutations associated with the prognosis of BCR::ABL1 -negative MPNs such as ASXL1 , EZH2 , IDH1/2 , SRSF2 , and U2AF1 . Furthermore, single-cell analyses have partially elucidated the effect of the order of mutation acquisition on the phenotype of BCR::ABL1 -negative MPNs and the mechanism of the pathogenesis of BCR::ABL1 -negative MPNs. Recently, specific CREB3L1 overexpression has been identified in megakaryocytes and platelets in BCR::ABL1 -negative MPNs, which may be promising for the development of diagnostic applications. In this review, we describe the genetic mutations found in BCR::ABL1 -negative MPNs, including the results of analyses conducted by our group.