Sunday, March 2, 2008

Discovering Early Molecular Determinants of Leukemogenesis

Link to the full text of this article can be found here:

Discovering early molecular determinants of leukemogenesis.

Departments of Medicine and Molecular and Medical Genetics, Oregon Health and Sciences University, and Northwest Veterans Affairs Cancer Research Center, Portland, Oregon, USA.
Truncating mutations of the G-CSF receptor are found during disease course in nearly half of all patients with severe congenital neutropenia. In this issue of the JCI, Liu et al. demonstrate that these mutations confer a competitive clonal advantage upon HSCs in mice and that the advantage is conditional because it is observed only in the presence of the ligand G-CSF (see the related article, doi:10.1172/JCI32704). Once activated, the mutant receptor requires the function of Stat5 in order to effect clonal expansion of this stem cell population. The results support the notion that early molecular steps in this and other neoplastic processes represent adaptations in which, through somatic mutations, "unfit" stem cells gain a measure of fitness by altering their relationships with their microenvironment.