The Myeloid Nuclear Differentiation Antigen (MNDA) regulates RNA processing and thereby influences the survival of chronic lymphocytic leukemia (CLL) cells
Dr. Milot’s group particularly focuses on the investigation of factors abnormally regulated or mutated in hematological malignancies, including leukemia. Among these is the Myeloid Nuclear Differentiation Antigen (MNDA), which is a stress-induced protein that promotes degradation of the anti-apoptotic factor MCL-1 and apoptosis in neutrophils.
MNDA is also expressed in B-cell clones isolated from individuals with CLL, a disease characterized by abnormal apoptosis control. While clinical data indicated that higher MNDA expression levels in CLL cells is associated with a better clinical course, the function and effect of the expression of MNDA remained to be defined. Furthermore, MNDA expression levels inversely correlate with the amount of the anti-apoptotic proteins MCL-1 and BCL-2 in human CLL samples.
In response to chemotherapeutic agents that induce genotoxic stress, MNDA nuclear localization is modified. It then affects the transcriptional competence of RNA Polymerase II and influences the Mcl1 and Bcl2 (pre-) mRNAs RNA synthesis and processing. Results indicate that it favors the rapid and dynamic tuning of Mcl1 and Bcl2 RNA levels and is required for the nucleation of a post-transcriptional mechanism of apoptosis control in CLL cells.