acute myeloid leukemia

Byaibio

Acute myeloid leukemia (AML) is a hematologic malignancy and a major disease context for therapy development, including epigenetic, metabolic, kinase, and immunotherapy approaches. It is notable for highly prevalent idh mutations and for genome-wide risk loci at 1q23.3, 2p23.3, 2q33.3, and 2p21, with 2p23.3 also associated with patient survival. Recent work highlights dc551040 as a potent, selective LSD1 inhibitor with promising combination activity, and homoharringtonine as an approved anti-leukemia drug used in AML combination therapy. Immunotherapy advances include natural killer cell therapy and sar445419 in relapsed or refractory AML, as well as anti aml drug candidate and dc551040 as therapeutic candidates in preclinical and early clinical settings. Mechanistically, AML studies also support natural killer cell-mediated killing after Siglec-7/9 blockade and dual mertk/FLT3 inhibition as a rational drug strategy.

Genetic risk and molecular subtypes

  • Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences AML risk; 1q23.3 was linked to AML with deletions of chromosome 5 and/or 7, while 2p21 and 2q33.3 were associated with cytogenetically complex AML. (PMID:41610418)
  • 2p23.3 was identified as a genome-wide significant risk locus for pan-AML and was also significantly associated with patient survival. (PMID:41610418)
  • idh mutations are highly prevalent in AML and are a major therapeutic focus for IDH inhibitors. (PMID:41821663)
  • A 2026 Blood study (PMID:41610418) supports shared inherited susceptibility across pan-AML and disease subgroups. (PMID:41610418)

Targeted therapy and epigenetic/metabolic inhibition

  • dc551040 was described as a potent and selective LSD1 inhibitor with promising combination therapy activity in AML. (PMID:41872160)
  • DC551040 showed good tolerability in a Phase I AML clinical trial. (PMID:41872160)
  • anti aml drug candidate lead compound 31l was described as a potential anti-AML drug candidate. (PMID:41872160)
  • A 2026 review on IDH enzyme inhibition summarized mechanisms, mutational insights, and effects of IDH inhibitors in AML. (PMID:41821663)
  • mertk/FLT3 dual inhibition was explored as a therapeutic strategy in AML. (PMID:41620146)

Immunotherapy and cell therapy

  • natural killer cell therapy was evaluated in participants with relapsed or refractory AML in a phase I, single-arm, open-label, dose-escalation multicenter study of the off-the-shelf allogeneic NK product sar445419. (PMID:41963545)
  • sar445419 was studied specifically in relapsed or refractory AML, extending NK-cell therapy into an ex vivo expanded allogeneic product format. (PMID:41963545)
  • A 2026 review of natural killer cell-based approaches noted that AML cell-line and patient-derived cell killing increased when Siglec-7 and/or Siglec-9 were blocked. (PMID:41928453)
  • Preclinical CAR-T advances in AML emphasized target iteration and microenvironment regulation, and a nanobody-based TCR-like CAR-T targeting PRAME was proposed for AML. (PMID:41800605; PMID:41985065)