According to a study from France, chronic lymphocytic leukemia (CLL) cell survival is promoted by high Mda-7 expression

08-10-2006

"CLL-B-cells are quiescent differentiated cells that produce interleukin (IL)-10 and accumulate due to resistance to apoptosis. The mechanisms underlying such resistance are poorly understood," wrote A. Sainz-Perez and colleagues, University of Paris 11.

"Herein we show that all CLL B-cells tested (30/30) display high mRNA and protein expression of the tumor suppressor Mda-7/IL-24, an IL-10 family member, in comparison to normal B cells. A downstream Mda-7 signaling target, p38 mitogen-activated protein kinase (MAPK) was highly phosphorylated in all CLL cells but not in normal B-cells.

"Mda-7 expression and p38 MAPK phosphorylation diminished in culture and the latter could be reinduced by recombinant (r)-IL-24 or LPS and Mda-7 transfection. Mda-7/IL-24 siRNA specifically inhibited p38 MAPK phosphorylation in CLL without affecting p38 MAPK, bcl2, or Lyn expression, further demonstrating the direct role of Mda-7/IL-24 in p38 MAPK activation."

The authors wrote, "Both pharmacological inhibition of p38 MAPK and Mda-7 silencing augmented spontaneous apoptosis by three-fold in CLL cells cultured in autologous serum, which was reversed by LPS and r-IL-24."

"We established the role of p38 MAPK in CLL cell survival and demonstrated a paradoxical effect, whereby Mda-7 and IL-24, inducers of apoptosis in diverse cancer cells, promote the survival of CLL B-cells through p38 MAPK activation," concluded the investigators.

Sainz-Perez and colleagues published their study in Leukemia (High Mda-7 expression promotes malignant cell survival and p38 MAP kinase activation in chronic lymphocytic leukemia. Leukemia, 2006;20(3):498-504).

For more information, contact A. Dalloul, University of Paris 11, Unite 131, INSERM, 32 Rue Carnets, F-92140 Clamart, France.

This article was prepared by Cancer Vaccine Week editors from staff and other reports. Copyright 2006, Cancer Vaccine Week via NewsRx.com.