The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jul 2

PMID 34202238

Citations 9

Authors

Samantha Bruno

Manuela Mancini

Sara De Santis

Cecilia Monaldi

Michele Cavo

Simona Soverini

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.

Citing Articles

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

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Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia.

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High CD44 expression and enhanced E-selectin binding identified as biomarkers of chemoresistant leukemic cells in human T-ALL.

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PMID: 39580584 PMC: 11794132. DOI: 10.1038/s41375-024-02473-7.

High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias.

Salwa A, Ferraresi A, Vallino L, Maheshwari C, Moia R, Gaidano G Int J Mol Sci. 2024; 25(21).

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