Discovering early molecular determinants of leukemogenesis.

Department of Medicine and Molecular and Medical Genetics, Oregon Health and Sciences University, Oregon, USA.
Journal of Clinical Investigation (Impact Factor: 12.81). 04/2008; 118(3):847-50. DOI: 10.1172/JCI35109
Source: PubMed

ABSTRACT 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 beginning on page 946). 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.

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