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.

In this study, the authors investigated the molecular mechanisms controlling the generation of HSCs during the intra-embryonic wave of haematopoiesis in the AGM and demonstrate a prominent role for the transcriptional repressors GFI1 and GFI1B in this process.

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.

The epigenetic factors KAT6A and KMT2A interact in normal hematopoiesis to regulate progenitors’ self-renewal. Authors evaluated the potential of different KAT6A therapeutic targeting strategies to alter the growth of KAT6A and KMT2A rearranged AMLs.

Here, the authors construct a comprehensive atlas of the endothelial-to-haematopoietic transition (EHT) continuum, as well as the subaortic niche cells in mouse embryonic aorta using a set of haemogenic endothelium (HE) reporter models.

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).

• FOXC1 contributes to a monocyte-macrophage lineage differentiation block in AML • FOXC1 and RUNX1 colocalize on chromatin via interaction of their DNA binding domains • A FOXC1/RUNX1/TLE3 repressor complex limits monocyte gene enhancer activity • FOXC1 depletion in AML initiates widespread redistribution of RUNX1/TLE3 on chromatin

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.

EP300/CBP are histone acetyltransferases recruited onto chromatin by oncogenic transcription factors and control the transcriptional program via their activity in enhancer areas. Nicosia et al. offer new promise in targeting EP300/CBP using the small-molecule inhibitor CSS1477 in patients with blood tumours and no other therapeutic options.