Its regulation of histone modification affects hematopoietic stem cell pool maintenance and its loss causes severe defects in HSC development [71, 72]. ASXL1 mutations are more common in the aberrant karyotypes, the elderly, and MDS-associated and secondary AML [73–77], while 9–12% of ASXL1 mutations are detected in cytogenetically normal AML [75–77]. NPM1 and ASXL1 mutations appear to be mutually exclusive [76–78]. The gene discussed is NPM1; the disease is acute myeloid leukemia.