Published CIRM-sponsored CSC research

Found via: Stem Cell Research by CIRM Grantees:

Cancer
Mutation Revealed to Convert Blood Stem Cells to Cancer Stem Cells

CIRM-funded researcher: Wei Guo

Researchers at UC, Los Angeles discovered a series of mutations that can convert normal blood stem cells into cancer stem cells. It is believed that many types of cancer result from cancer stem cells created by such mutations. In this case the first mutation converted normal stem cells and then caused over expression of an oncogene, a cancer gene, resulting in a proliferation of leukemia stem cells and acute T-cell lymphoblastic leukemia in a mouse model. The team hopes that by studying these pathways they will find ways to block them with small molecule drugs and cure the often fatal disease. The study was published in the May 22, 2008 issue of Nature.

Related Information: Nature paper, UCLA press release, The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, Funding grant summary

The published paper is: Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation by Wei Guo and 10 co-authors, including Hong Wu, Nature 2008(May 22); 453(7194): 529-33 Epub 2008 May 7. [PubMed Citation].

Clonal origins of relapsed ALL

Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia by Charles G Mullighan and 6 co-authors, including James R Downing, Science 2008(Nov 28); 322(5906): 1377-80. PubMed Abstract:

Most children with acute lymphoblastic leukemia (ALL) can be cured, but the prognosis is dismal for the minority of patients who relapse after treatment. To explore the genetic basis of relapse, we performed genome-wide DNA copy number analyses on matched diagnosis and relapse samples from 61 pediatric patients with ALL. The diagnosis and relapse samples typically showed different patterns of genomic copy number abnormalities (CNAs), with the CNAs acquired at relapse preferentially affecting genes implicated in cell cycle regulation and B cell development. Most relapse samples lacked some of the CNAs present at diagnosis, which suggests that the cells responsible for relapse are ancestral to the primary leukemia cells. Backtracking studies revealed that cells corresponding to the relapse clone were often present as minor subpopulations at diagnosis. These data suggest that genomic abnormalities contributing to ALL relapse are selected for during treatment, and they point to new targets for therapeutic intervention.