Protein renews stem cells, leukemia

Two mouse embryos at 14.5 days. Control embryo on the left. Right, a "bloodless" embryo lacking expression of the Lis1 protein. Loss of the protein proved fatal before birth in a study led by UCSD scientists.

A protein called Lis1 is required for both hematopoietic stem cell formation and leukemia cells, according to a new study led by UCSD researchers.

Drugs that target this protein could provide more effective chemotherapy, the researchers say in their study. Performed in mice and in human leukemia cells, the study was published online Sunday in the journal Nature Genetics. Tannishtha Reya, a UCSD Dept. of Pharmacology professor, was senior author. Bryan Zindahl and Takahiro Ito were first authors.

The discovery underscores the close relationship between stem cells and cancer, as both require self-renewal.

Deletion of Lis1 from mouse hematopoietic stem cells caused excessive differentiation, depleting the reserve of undifferentiated stem cells, the study found. The lack of a reserve eventually resulted in loss of specialized blood-forming stem cells, resulting in what researchers called a "bloodless mouse." The defect was lethal, of course; none of the mouse embryos created survived to birth.

The study also examined mouse leukemia models in which Lis1 was turned off. Control mice given blast-crisis CML and treated with tamoxifen all died. None of similar mice given the same leukemia, but with cells engineered to lose Lis1 expression, actually developed leukemia.

"Our work shows that elimination of Lis1 potently inhibits cancer growth, and identifies Lis1 and other regulators of protein inheritance as a new class of molecules that could be targeted in cancer therapy," Reya said in a UCSD press release.

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Protein renews stem cells, leukemia