Daratumumab inhibits acute myeloid leukaemia metabolic capacity by blocking mitochondrial transfer from mesenchymal stromal cells
Jayna J. Mistry, Jamie A Moore, Prakrit Raj Kumar, Christopher R. Marlein, Charlotte Hellmich, Genevra Pillinger, Aisha Jibril, Federica Di Palma, Angela Collins, Kristian M. Bowles, Stuart A. Rushworth
Abstract
Acute myeloid leukemia (AML) proliferation is dependent on a complex multi-faceted interplay between the blasts and the bone marrow (BM) microenvironment. 1 We and others have previously demonstrated that functional mitochondria are transferred from the mesenchymal stem cells (MSC) to the AML blasts facilitating progression of the disease, 2,3 in a process which is hijacked from hematopoietic stem cell response to infection. 4 Clinical observation trials using venetoclax, which targets BCL2 (which in turn is a key regulator of the mitochondrial apoptotic pathway), in combination with hypomethylating agents showed tolerable safety and favorable overall response rate in elderly patients with AML. 5 Taken together, these data imply that mitochondria represent an attractive and biologically plausible drug target in the treatment of AML.