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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Monday, April 25, 2022
Thierry Fest, MD, PhD, of the University Hospital of Rennes, France, and colleagues identified a cell-autonomous function that seems to link kinase activity to the newly acquired secretion ability of plasmablasts. Their findings, which were published in the journal Blood, may prompt the reconsideration of proviral integrations of Moloney virus 2 (PIM2) as a therapeutic target in patients with multiple myeloma.
“Our present results showed that the final transcriptional modifications in B cells committed to differentiation into plasmablasts are associated with the expression of a set of crucial genes, including PIM2. The newly established adaptive status of the generated plasmablasts is maintained in mature plasma cells,” the investigators remarked. “Lastly, we showed that PIM2 kinase’s antiapoptotic effects should be further investigated in the context of novel treatment strategies in multiple myeloma.”
The investigators conducted several laboratory assessments to evaluate the effects of PIM2 on plasmablast generation and plasma cell survival. Based on the results of in vitro inhibition experiments, the early, sustained upregulation of PIM2 kinase appeared to be pivotal during human B-cell differentiation; it was found to continue in both mature normal and malignant plasma cells in the bone marrow.
Mechanistically, PIM2 seemed to sustain the G1/S phase transition by acting on CDC25A and p27Kip1 and hindering caspase 3–driven apoptosis through BAD phosphorylation and cytoplasmic stabilization of p21Cip1. Interleukin 6 appeared to trigger PIM2 expression in plasma cells; according to the investigators, this resulted in the antiapoptotic effects on which malignant plasma cells are dependent. Pan-PIM and MCL1 inhibitors demonstrated synergistic activity in multiple myeloma.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
