Advances in the Pathogenesis and Treatment of Acute Myeloid Leukemia—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 198

Special Issue Editor


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Guest Editor
Onco Hematology, Department of Oncology, Veneto Institute of Oncology, IOV-IRCCS, 31033 Padua, Italy
Interests: acute myeloid leukemia; hematopoietic stem cell transplantation; target therapies; bone marrow microenvironment
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Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is an extremely heterogeneous disease and remains difficult to treat. A better understanding of the AML biological landscape is allowing the development of new target therapies and biological strategies that are opening up new possibilities, even in unfavorable populations such as relapse/refractory or older patients. This new therapeutic armamentarium includes Bcl-2 inhibitors, FLT3 inhibitors, IDH1-2 inhibitors, and many other small synthetic molecules. The recognition of specific gene mutations, as well as the identification of peculiar signature pathways, such as Homeobox gene A and B overexpression, can help in the identification of shared therapeutic targets, as is currently the case for Menin inhibitors. Interactions between AML blasts and the microenvironment and the remaining immune compartment are still poorly understood and could partially explain the largely heterogeneous course of the disease, even in the era of new target therapies. The rational use of these compounds in clinical practice cannot, therefore, disregard a better understanding of resistance and immune-escape mechanisms.

This Special Issue will be dedicated to recent progress in understanding the pathogenetic AML landscape and possible therapeutic strategies. We invite authors to submit original research and review articles. Suitable topics include, but are not limited to, the following:

  • Potential targeted therapies and combination strategies in acute myeloid leukemia;
  • The pathogenesis of acute myeloid leukemia;
  • The bone marrow microenvironment in acute myeloid leukemia;
  • Precision medicine in acute myeloid leukemia;
  • Mechanisms of resistance.

Dr. Alessandra Sperotto
Guest Editor

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Keywords

  • acute myeloid leukemia
  • target therapies
  • molecular pathogenesis
  • biological therapy
  • precision medicine

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Published Papers (1 paper)

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Review

41 pages, 3565 KB  
Review
Pandora’s Box of AML: How TP53 Mutations Defy Therapy and Hint at New Hope
by Elyse A. Olesinski and Shruti Bhatt
Biomedicines 2025, 13(12), 3007; https://doi.org/10.3390/biomedicines13123007 - 8 Dec 2025
Abstract
TP53 mutations are among the worst prognostic factors in acute myeloid leukemia (AML), with affected patients facing relapse-free survival of just five-to-six months compared to TP53 wild-type patients. A major barrier to improving outcomes lies in the dearth of effective therapies, as TP53 [...] Read more.
TP53 mutations are among the worst prognostic factors in acute myeloid leukemia (AML), with affected patients facing relapse-free survival of just five-to-six months compared to TP53 wild-type patients. A major barrier to improving outcomes lies in the dearth of effective therapies, as TP53 mutant patients remain refractory to conventional cytotoxic chemotherapies, targeted therapies, and even allogeneic stem cell transplantation. In this review, we first summarize current clinical strategies and the major setbacks of p53 activators, MDM2/X regulators, and immunotherapy, highlighting the disconnect between promising pre-clinical studies and limited durable clinical responses. We next discuss the mechanisms of therapy resistance in TP53 mutant AML, with specific emphasis on dysfunction in the mitochondrial apoptotic pathway and clonal evolution of TP53 mutant hematopoietic stem cells. We then outline a roadmap for developing tailored therapies that may finally redefine prognosis for this high-risk patient population, including apoptotic activators, cell-cycle modulators, and immune- and metabolic-based therapies. We lastly call attention to new biomarker-driven approaches that can improve patient stratification and optimize identification of responders. By connecting mechanistic understanding with translational insights, this review underscores both the formidable challenges and the emerging opportunities in TP53 mutant AML. Full article
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