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Acute Myeloid Leukemia-Osteoblast Interaction Mediated Autophagy Induction Protects Against Cytarabine Induced
Kamini Shivhare1,2, Neeraj Kumar Satija1,2
1Systems Toxicology Group, Food, Drug & Chemical, Environment and Systems Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
Abstract:
High rate of relapse, following chemotherapy, in acute myeloid leukemia (AML) is a major concern. The chemoprotection conferred by the bone marrow microenvironment has lately been recognized, in addition to autophagy-mediated chemoresistance. Thus, the present study explored the effect of osteoblast on autophagy in AML and its impact on sensitivity to cytarabine (Ara-C) in the context of endosteal niche. Co-culture of KG1-a, HL60, or THP-1 AML cells with osteoblastic Saos-2 cell line induced autophagy in AML cell lines under direct contact. HL60 cells when co-culture with Saos-2 demonstrated more resistance to Ara-C induced apoptosis, which was reversed upon chloroquine treatment. Similarly, inhibition of autophagy in AML cell by knocking down Beclin-1 enhanced HL60 sensitivity to Ara-C. An interesting observation was upregulation of autophagy even in Saos-2 cells upon co-culture with AML cell, and increase in HL60 apoptosis in response to Ara-C on Beclin-1 knockdown in osteoblast cell. This highlights that autophagy plays a chemoprotective role in the endosteal niche in AML against Ara-C.
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