Acute Myeloid Leukemia Clinical Strategies

Acute myeloid leukaemia (AML) represents a heterogeneous group of aggressive myeloid neoplasms characterised by clonal expansion of poorly differentiated myeloid blasts. Clinical strategies hinge on precise risk stratification, integrating cytogenetic and molecular profiling with patient fitness to guide therapeutic intensity. Standard induction regimens remain anchored in cytarabine and anthracycline combinations, while allogeneic stem cell transplantation offers curative potential in eligible patients. Over the past five years, the emergence of targeted agents—such as FLT3 and IDH inhibitors—has reshaped frontline and salvage approaches, especially for genetically defined subgroups. Measurable residual disease (MRD) monitoring has become central to assessing depth of response and informing post-remission interventions. Personalized ex vivo drug sensitivity platforms and novel epigenetic therapies aim to refine regimen selection further. Supportive care improvements, including antimicrobial prophylaxis and transfusion strategies, have bolstered tolerance of intensive therapies. Globally, efforts focus on broadening access to genomic diagnostics, harmonising MRD assessment, and developing low-intensity regimens for frail or elderly patients.

Research from Nature Portfolio

Phase 1 clinical investigation of an oral menin inhibitor has demonstrated promising activity in relapsed or refractory AML harbouring KMT2A rearrangements or NPM1 mutations. Treatment was well tolerated, produced differentiation of leukaemic blasts, achieved measurable residual disease clearance in a subset of patients and established menin inhibition as a viable epigenetic strategy. Concurrently, advances in quantitative drug sensitivity scoring (DSS) algorithms have enabled systematic integration of high-throughput ex vivo dose–response data. This approach accurately distinguishes patient-selective drug responses, supports dynamic monitoring of emerging resistance and offers a framework for tailoring combination regimens to individual AML samples.

Acute Myeloid Leukemia Clinical Strategies publication trend

The graph below shows the total number of articles in acute myeloid leukemia clinical strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Menin–KMT2A interaction: A critical epigenetic complex driving aberrant transcription in AML with KMT2A rearrangements.

Measurable residual disease (MRD): Low-level persistence of leukaemic cells detectable by sensitive molecular or flow cytometric assays beyond morphological remission.

Clonal haematopoiesis: Age-related expansion of haematopoietic stem cell clones bearing somatic mutations, which may predispose to AML.

Drug sensitivity score (DSS): A quantitative metric integrating multiple dose–response relationships to assess ex vivo efficacy and guide personalised therapy selection.

References

1. Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes. Signal Transduction and Targeted Therapy (2023).
2. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature (2023).
3. Acute myeloid leukemia: current progress and future directions. Blood Cancer Journal (2021).
4. 2021 Update Measurable Residual Disease in Acute Myeloid Leukemia: European LeukemiaNet Working Party Consensus Document. Blood (2021).
5. Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Scientific Reports (2014).