Bone marrow stromal cell mitochondrial biology modulates mitochondrial transfer to leukemic blasts in acute myeloid leukemia
Marta Pera1, Mario Barilani1,2, Marta Dossena1, Luana Santana-Gomes1, Beatrice Colombo1, Alessandro Cherubini1, Giuseppe Buono1, Francesca Salanitro1, Lorenza Lazzari1 1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Milano (Italy); 2Università degli studi di Milano. Milano (Italy)
Acute myeloid leukemia (AML) is an aggressive bone marrow derived blood cancer where intercellular communication in the leukemic bone marrow participates in disease development, progression and chemoresistance. Despite the existing cytotoxic treatments directly targeting the leukemic cells, the overall outcomes for AML patients remain poor and most patients die of relapse. The bone marrow microenvironment consists of many cell types broadly classed as bone marrow stromal cells (BMSCs) that have been recently shown to donate their mitochondria within the bone marrow niche contributing to the chemotherapy resistance of the AML blasts. Contrary to the Warburg hypothesis, AML blasts rely on mitochondrial oxidative phosphorilation for survival. At this time, however, the mechanisms facilitating the transfer remain poorly defined and the stimuli for transfer unknown.
Hitherto most of the studies have been focused in leukemic cells but BMSCs, their counterparts in the transfer, have received almost no attention. In our study the aim is to understand what happens to the BMSC mitochondrial compartment in response to chemotherapy and to the interaction with leukemic cells. Defining and understanding these changes happening in the donor cells is crucial to unravel the mechanism that triggers mitochondrial transfer in AML.
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