Treating leukemia at the risk of inducing severe anemia.

Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-13347) presented data indicating that cell type-specific pathway cross-talk is likely an important mechanism to consider. Shp2 and Pten, two master regulators of central cytoplasmic signaling pathways, oppose each other in myeloproliferation and leukemogenesis, but cooperate in promoting erythropoiesis. Thus, genetic ablation or pharmacologic inhibition of Shp2 suppresses the leukemogenic effect of Pten loss, yet simultaneously induces severe anemia in mice with Pten deficiency in blood cells.