[Cell-biology] Regulating Hematopoietic Stem Cell Homeostasis And Leukemogenesis

biospace via cellbiol%40net.bio.net (by biospace from noster-it.com)
Wed Jan 21 01:24:52 EST 2009

Dr. Richard Flavell (Yale University) and colleagues identify the c-
Cbl protein as a critical repressor of hematopoietic stem cell (HSC)
self-renewal. In addition to establishing a key role for protein
ubiquitylation in HSC development, this finding posits c-Cbl as a
potential target in research into stem cell engineering as well as
cell-based leukemia treatments.
Dr. Flavell describes the work as elucidating "a novel dimension in
our understanding the self-renewal of Hematopoietic stem cells."

Like all stem cell populations, HSC reply upon asymmetric cell
division to generate two different daughter cells: one future stem
cell, and another cell that will further differentiate into a more
specialized cell type. Thus, a balance is struck between the
production of new cell types and the renewal of the stem cell pool.
However, imbalances between HSC self-renewal and differentiation can
lead to hematologic malignancies like leukemia.

Dr. Flavell's group discovered that the E3 ubiquitin ligase, c-Cbl,
suppresses HSC self-renewal. The researchers generated transgenic mice
deficient in c-Cbl, and demonstrated that these c-Cbl-mutant mice
display an increased number of HSCs.
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