Acute lymphoblastic leukemia (ALL) is the commonest form of childhood cancer and results from clonal proliferation of transformed hemopoietic cells, caused by genetic alterations. Most cases arise from B-cell clones arrested at the pre–B-cell stage of differentiation, but the molecular events involved have been unclear. In the May 22 Nature, Hassan Jumaa and colleagues at the University of Freiburg show that the somatic loss of the adaptor protein SLP-65 is one of the primary causes of childhood pre-B ALL (Nature, 423:452-456, May 22, 2003).

Jumaa et al. used retroviral vectors and expressed a green fluorescent–SLP-65 fusion protein in SLP-65^-/- pre–B-cell lines. They observed that reconstitution of the SLP-65 expression in these cells enhanced differentiation in vitro and prevented the development of pre–B-cell leukemia when the cells were injected into immune-deficient mice. In addition, they showed that 16 of the 34 childhood pre-B ALL samples tested had a...