p38α/β inhibition prevents ALL proliferation in vivo

P38α/β stress-activated protein kinase has been described as an important regulator of dormancy and tumor cell dissemination in different epithelial malignancies. However, p38α/β also regulates other cellular processes such as inflammation, apoptosis and, rarely, cell cycle progression. Here, we study the role of p38α/β as a targetable mediator of acute lymphoblastic leukemia (ALL) proliferation.

P38α/β was highly phosphorylated during log-phase of ALL cell growth in culture. Importantly, intracellular flow cytometric analyses found that high phosphorylation of p38α/β correlated with the S- and G2/M-phases of the cell cycle. Remarkably, maximal p38α/β activation was found in ALL cells proliferating in permissive microenvironments in avian xenografts. Inhibition of p38α/β with SB203580 and BIRB-796 markedly suppressed engraftment and proliferation in vivo.

We thus propose p38α/β as a mediator of growth-stimulatory mechanisms in ALL cells and suggest p38α/β inhibition as a potential adjunct therapeutic approach in the treatment of the disease.