NPM1 Biology in Myeloid Neoplasia

AbstractPurpose of ReviewNucleophosmin (NPM1) mutations are encountered in myeloid neoplasia and are present in ~  30% of de novo acute myeloid leukemia cases. This review summarizes features of mutantNPM1-related disease, with a particular emphasis on recent discoveries relevant to disease monitoring, prognostication, and therapeutic intervention.Recent FindingsRecent studies have shown thatHOX/MEIS gene overexpression is central to the survival ofNPM1-mutated cells. Two distinct classes of small molecule drugs, BH3 mimetics and menin-MLL interaction inhibitors, have demonstrated exquisite leukemic cell toxicity in preclinical AML models associated withHOX/MEIS overexpression, and the former of these has shown efficacy in older treatment-na ïveNPM1-mutated AML patients. The results of ongoing clinical trials further investigating these compounds will be of particular importance and may alter the clinical management of patients withNPM1-mutated myeloid neoplasms.SummarySignificant scientific advancements over the last decade, including improved sequencing and disease monitoring techniques, have fostered a much deeper understanding of mutantNPM1 disease biology, prognostication, and opportunities for therapeutic intervention. These discoveries have led to the development of clinical assays that permit the detection and monitoring of mutantNPM1 and have paved the way for future investigation of targeted therapeutics using emerging cutting-edge techniques.
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research