Can increased cytokine receptor signaling cause leukemia?
Models of leukemic transformation have focused on binary phenomena: either loss of function of tumor suppressors or gain of function via high-level, dysregulated expression of a dominant transforming oncogene or an abnormal oncogenic fusion protein. The AKR/J mouse is a model of susceptibility to T-lymphoid malignancies. AKR mice develop thymic lymphomas spontaneously or rapidly after neonatal challenge with transforming murine retroviruses, such as the T-lymphomagenic strain SL3-3.1 The mechanisms of increased susceptibility to transformation of AKR lymphohematopoietic progenitors are unknown. On page 1985 of the present issue of Blood, Laouar and colleagues describe differences in expression of a cytokine receptor, the interleukin 7 receptor (IL-7R), between thymocytes from AKR mice and other strains not prone to lymphoma. The IL-7R is composed of the IL-7R and common gamma chain (c) subunits. Signal transduction through the IL-7R, like other c-containing receptors (IL-2R, IL-4R, IL-
