A Stat5 flashback

Stat5a and b have given immunologists mixed messages. Nearly a decade of work pointed to a central role for these transcription factors in T- and B-cell development as well as development of some leukemias, but an N-terminal deletion knockout made in the late 1990s produced relatively mild effects. Recent work on a full-length knockout in mice falls much more in line with what the community had expected.

One group doing the work contains members who had previously contended with the puzzling phenotypes, a fact that Kendall Smith, Chief of Immunology at Weill Medical College, Cornell University, finds gratifying.

"The nice thing is the fact that the same people who published the original KO findings have gone back and said, 'You know, we need to look at this again.' This time they knocked out all of the exons from both Stat5 a and b and now they have severe phenotypes in T-cell and B-cell development.

"It looks like Stat5 is also probably the key molecule that's phosphorylated by the Ableson kinase that leads to uncontrolled growth, transformation, and malignancy. That impacts ... on the transformation in CML [chronic myelogenous leukemia] as well as ALL [acute lymphocytic leukemia] that are Philadelphia Chromosome positive."