Our latest work : “Upregulation of ALDH1 as an adaptive epigenetic response to anthracyclines in acute myeloid leukemia” has just been published in HemaSphere.
This study reveals how ALDH1A1 and ALDH1A2 are upregulated as part of an adaptive stress response to anthracycline chemotherapy in AML. We show that STAT3 and FOS/JUN transcription factors activate ALDH1 enhancers under anthracycline stress, promoting resistance to daunorubicin.
Importantly, co-treatment with the ALDH1 inhibitor DIMATE (ABD3001) restored chemosensitivity in vitro and in vivo, providing a strong preclinical rationale for combining ALDH1 inhibitors with standard therapies to overcome drug resistance.
These findings have potential implications for relapsed/refractory AML and secondary AML—particularly in patients with a history of anthracycline exposure or genetic backgrounds that enhance STAT3 signaling (e.g., JAK-pathway, epigenetic/spliceosome alterations, or TP53 mutations).
