With funding from Blood Cancer UK, Mark Willams and Robert Wynn are setting up a clinical trial that aims to transform stem cell transplantation and offer new hope for many young adults with AML.

Somerville et al. report frequent derepression of FOXC1 in human acute myeloid leukemia in association with the HOXA/B locus. FOXC1 contributes to monocyte lineage differentiation block and enhanced clonogenic potential and collaborates with HOXA9 to accelerate leukemia onset in vivo.

Maiques-Diaz et al. report that, while LSD1 inhibitors target both scaffolding and enzymatic functions of the protein, drug-induced myeloid leukemia cell differentiation is primarily due to the disruption and release from enhancers of GFI1/CoREST complexes, leading to the activation of subordinate myeloid transcription factor genes.

Leukaemic fusion proteins drive leukaemia by maintaining abnormal transcriptional networks. This study demonstrates the feasibility of epigenomics-instructed screens for identifying oncogene-driven vulnerabilities and their exploitation by repurposed drug approaches.

Morphologic response to treatment with iadademstat. (A) Representative images of blood smears showing morphologic differentiation from patient 28 (top) at screening (left) and cycle 1(C1), day 21 (D21) (right) and patient 31 (bottom) at screening (left) and C1D14 (right; two images from the same slide and patient are shown, separated by a dotted line).

Resistance to chemotherapy is the most common cause of treatment failure in AML and drug efflux pump ABCB1 is a critical mediator. We established an experimental system and analysis pipeline to determine whether promoter translocations account for high ABCB1 expression in cases of relapsed human AML.