In vitro experiments suggest that platelets and their mitochondrial respiratory function may be involved in regulating MM cell proliferation, metabolic reprogramming, and mitochondrial dynamics.
Key Findings
Results
Platelets from MM patients showed increased activation marker CD41/CD61 expression compared to healthy volunteers.
CD41/CD61 expression was (2.10 ± 1.15)% in MM patients vs (0.22 ± 0.19)% in healthy volunteers (P=0.048)
CD42b expression was decreased in MM patients: (52.80 ± 8.73)% vs (74.58 ± 5.11)% in healthy volunteers (P=0.020)
Platelet activation and mitochondrial ROS levels were assessed by scanning and transmission electron microscopy and flow cytometry
Peripheral blood was collected from newly diagnosed MM (NDMM) patients at Sichuan Provincial People's Hospital between January 2020 and December 2023
Results
Mitochondrial reactive oxygen species (ROS) levels in platelets were significantly elevated in MM patients compared to healthy volunteers.
Mitochondrial ROS levels: 150.50 ± 17.79 in MM patients vs 62.45 ± 21.34 in healthy volunteers (P=0.001)
ROS levels were assessed by flow cytometry
Results
Serum levels of multiple platelet-related factors were altered in MM patients compared to healthy volunteers.
IL-34 and platelet factor 4 (PF4) levels were reduced in MM patients (P<0.05)
bFGF, IGF-1, IL-6, P-selectin, PDGF, and TGF-β1 levels were all increased in MM patients (all P<0.05)
VEGF levels did not differ significantly between MM patients and healthy volunteers (P=0.086)
Serum factor levels were measured by ELISA
Results
Co-culture of MM cell lines with platelets for 48 hours promoted MM cell proliferation, and this effect was abolished when platelets were pretreated with mitochondrial respiratory inhibitors.
MM cell lines used were RPMI 8226 and U266
PLTs pretreated with rotenone (Complex I inhibitor) or oligomycin (ATP synthase inhibitor) lost the pro-proliferative effect (all P<0.001)
MM cell proliferation was assessed by the CCK-8 assay
Co-culture duration was 48 hours
Results
Co-culture with platelets increased mRNA expression of metabolism-related and mitochondrial dynamics-related genes in MM cells.
Metabolism-related genes upregulated: citrate synthase (CS) and lactate dehydrogenase A (LDHA) (all P<0.05)
Gene expression was quantified by real-time quantitative PCR (qPCR)
Results
Pretreatment with the Drp1 inhibitor Mdivi-1 suppressed DNM1L mRNA expression in MM cells, and subsequent co-culture with platelets reversed this inhibition.
Mdivi-1 pretreatment reduced DNM1L mRNA expression to 0.75 ± 0.16 vs 1.00 ± 0.09 in controls (P=0.002)
Subsequent co-culture with PLTs reversed the inhibition: 1.02 ± 0.13 vs 0.75 ± 0.16 (P=0.007)
Drp1 and phosphorylated Drp1 were analyzed by Western blot
Results
Co-culture with platelets increased phosphorylated Drp1 (p-Drp1 Ser616) protein levels in U266 MM cells.
p-Drp1 (Ser616) protein levels were increased in U266 cells after co-culture with PLTs (P<0.05)
Zhang L, Xiang Y, Li Y, Zhang J. (2026). [A preliminary study on the role of platelet mitochondria in the proliferation and metabolism of multiple myeloma cells].. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. https://doi.org/10.3760/cma.j.cn121090-20250616-00278