Fred Hutchinson Cancer Research Center
Dr. Weissman; Stephen R. Quake, PhD, professor of bioengineering; Norma Neff, PhD, research technical manager; and Dr. Majeti have continued collaborating with Philip Greenberg, MD, and Stanley Riddell, MD, professors of medicine at the Fred Hutchinson Cancer Research Center in Seattle, in efforts to determine the whole genome sequence of human acute myelogenous leukemia (AML) stem cells and non-stem cells from a single patient.
- They have now completed and analyzed the whole genome sequence of AML stem cells and non-stem cells from a single patient and found that, at the DNA sequence level, these two populations are identical. This finding is consistent with the idea that these cells are descended from, and genetically identical to, a single ancestor and support the cancer stem cell model. A number of single gene mutations were identified and confirmed. The products of those genes are candidates for the development of specific cytotoxic T cells, but the investigators’ work during this reporting period has focused on validation of the sequence variants and has not yet moved into T-cell responses. It is expected that these experiments could be joined with the studies on DCs described above.
- In parallel, Drs. Weissman, Riddell, and Majeti have advanced the analysis of AML stem cell-specific antigens. The goal of this analysis has been to identify the top candidates as the bases for, ultimately, developing cytotoxic T cells directed against AML stem cells. During this reporting period, they have focused heavily on bioinformatics analysis of candidate targets and have developed a short list of two or three top candidates. They are in the process of validating protein level expression by immunohistochemistry, because the candidates were chosen based on RNA expression.