Mitochondrial transfer in acute myeloid leukaemia and multiple myeloma: Mechanisms, consequences and potential therapeutic opportunities

Haematological malignancies, such as acute myeloid leukaemia (AML) and multiple myeloma (MM), which develop from malignant transformations within the bone marrow, represent the most critical unmet needs in the haemato-oncology field. Sub-optimal clinical outcomes in patients with AML and MM are often driven by resistance to chemotherapy. It is well established that cells within the bone marrow microenvironment (BMME) support the proliferation and survival of these blood cancer cells. One of the mechanisms by which these BMME-resident cells support the malignant cells is through horizontal mitochondrial transfer (HMT), a mechanism well documented as occurring under steady-state conditions as well as in many cancers. Recent research implicates mitochondrial transfer in BMME-driven chemoresistance in AML and MM. In this review, we critically analyse current understanding of the role of HMT in supporting the survival and proliferation of AML and MM cells, as well as driving resistance to cytotoxic effects of chemotherapy. We further elucidate various mechanisms, molecular triggers, functional consequences, and therapeutic implications for HMT in AML and MM. Our review also highlights unanswered questions within the HMT field and provides a theoretical basis for further study, giving direction on what is important in translating this knowledge into effective future therapeutic strategies.