LAUSR

In this issue of Blood, Garg et al report on their investigation of the molecular interaction between mutations affecting DNMT3A and NPM1, and internal tandem duplications (ITDs) of FLT3 in acute myeloid leukemia (AML). They found that when the 3 mutations cooccur in AML, they synergize to drive increased expression of hepatic leukemia factor (HLF), a transcription factor, and are associated with particular characteristics such as increased leukemic stem cell (LSC) frequency and an aberrant immunophenotype (GPR56highCD34low), which seem to be at least in part attributable to overexpression of HLF. Their findings establish HLF overexpression as an important mediator of the adverse phenotype and propose that HLF or its downstream effectors represent potential therapeutic vulnerabilities of this poor-prognosis AML subtype.1