Loss of Lamin B1 in Myeloid Neoplasms with 5q Deletion Causes Myeloid-Biased Hematopoiesis and Pelger-Huet Nuclear Anomaly

Hematopoietic stem and progenitor cells (HSPCs) acquire somatic mutations and cytogenetic abnormalities leading to myeloid neoplasms (MDS/AML). A subgroup of 10-20% MDS and AML cases undergo complex chromosomal rearrangements associated with TP53 mutations and poor prognosis. One of the most common chromosomal events in high-risk myeloid neoplasms is deletion of chromosome 5q (del(5q)). In contrast to 5q- syndrome, characterized by a distal commonly deleted region (CDR) and good prognosis, the critical CDR in high-risk MDS/AML centers on 5q31. However, the key genes in the high-risk 5q-deleted region that contribute to dysregulation of hematopoiesis, chromosomal instability, and disease progression remain poorly characterized.