Recently, it has become evident that mitochondrial transfer (MT) plays a crucial role
in the acquisition of cancer drug resistance in many hematologic malignancies; however,
for multiple myeloma, there is a need to generate novel data to better understand
this mechanism. Here, we show that primary myeloma cells (MMs) respond to an increasing
concentration of chemotherapeutic drugs with an increase in the acquisition of mitochondria
from autologous bone marrow stromal cells (BM-MSCs), whereupon survival and adenosine
triphosphate levels of MMs increase, while the mitochondrial superoxide levels decrease
in MMs. These changes are proportional to the amount of incorporated BM-MSC-derived
mitochondria and to the concentration of the used drug, but seem independent from
the type and mechanism of action of chemotherapeutics. In parallel, BM-MSCs also incorporate
an increasing amount of MM cell-derived mitochondria accompanied by an elevation of
superoxide levels. Using the therapeutic antibodies Daratumumab, Isatuximab, or Elotuzumab,
no similar effect was observed regarding the MT. Our research shows that MT occurs
via tunneling nanotubes and partial cell fusion with extreme increases under the influence
of chemotherapeutic drugs, but its inhibition is limited. However, the supportive
effect of stromal cells can be effectively avoided by influencing the metabolism of
myeloma cells with the concomitant use of chemotherapeutic agents and an inhibitor
of oxidative phosphorylation.
