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

International Journal of Molecular Sciences

Samantha Bruno¹  Simona Soverini¹  Michele Cavo¹  Sara De Santis¹  Cecilia Monaldi¹  Manuela Mancini² 

[1] Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy;

关键词: acute myeloid leukemia;    hypoxic bone marrow microenvironment;    metabolic reprogramming;    leukemic stem cell;   

DOI  :  10.3390/ijms22136857

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown