A Role for the Bone Marrow Microenvironment in Drug Resistance of Acute Myeloid Leukemia
Seyed Mohammadreza Bolandi,
Mahdi Pakjoo,
Peyman Beigi,
Mohammad Kiani,
Ali Allahgholipour,
Negar Goudarzi,
Jamshid S. Khorashad,
Anna M. Eiring
Affiliations
Seyed Mohammadreza Bolandi
Department of Immunology, Razi Vaccine and Sera Research Institute, Karaj, Iran
Mahdi Pakjoo
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Peyman Beigi
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Mohammad Kiani
Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj, Iran
Ali Allahgholipour
Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj, Iran
Negar Goudarzi
Department of Immunology, Razi Vaccine and Sera Research Institute, Karaj, Iran
Jamshid S. Khorashad
Centre for Haematology, Hammersmith Hospital, Imperial College London, London W12 0HS, UK
Anna M. Eiring
Center of Emphasis in Cancer, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, TX 79905, USA
Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis and remarkable resistance to chemotherapeutic agents. Understanding resistance mechanisms against currently available drugs helps to recognize the therapeutic obstacles. Various mechanisms of resistance to chemotherapy or targeted inhibitors have been described for AML cells, including a role for the bone marrow niche in both the initiation and persistence of the disease, and in drug resistance of the leukemic stem cell (LSC) population. The BM niche supports LSC survival through direct and indirect interactions among the stromal cells, hematopoietic stem/progenitor cells, and leukemic cells. Additionally, the BM niche mediates changes in metabolic and signal pathway activation due to the acquisition of new mutations or selection and expansion of a minor clone. This review briefly discusses the role of the BM microenvironment and metabolic pathways in resistance to therapy, as discovered through AML clinical studies or cell line and animal models.
