HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia.

KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM.

Inducible MLL-AF9 Expression Drives an AML Program during Human Pluripotent Stem Cell-Derived Hematopoietic Differentiation.

A t(9;11)(p22;q23) translocation produces the MLL-AF9 fusion protein, which is found in up to 25% of de novo AML cases in children. Despite major advances, obtaining a comprehensive understanding of context-dependent MLL-AF9-mediated gene programs during early hematopoiesis is challenging. Here, we generated a human inducible pluripotent stem cell (hiPSC) model with a doxycycline dose-dependent MLL-AF9 expression.

Identification of transcription factors dictating blood cell development using a bidirectional transcription network-based computational framework.

Advanced computational methods exploit gene expression and epigenetic datasets to predict gene regulatory networks controlled by transcription factors (TFs). These methods have identified cell fate determining TFs but require large amounts of reference data and experimental expertise. Here, we present an easy to use network-based computational framework that exploits enhancers defined by bidirectional transcription, using as sole input CAGE sequencing data to correctly predict TFs key to various human cell types.