In the February 13th online edition of PNAS, R. Majeti et al. from Stanford University's Inst. for Stem Cell Biol. and Regenerative Medicine conducted a study comparing the gene expression profiles of highly enriched normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The investigators reported from their study that 3,005 genes are differentially expressed between the two cell populations. The researchers found that multiple pathways such as Wnt signaling, MAP Kinase signaling, and Adherens junction are aberrantly regulated in LSCs. Surprisingly, ribosomal and T cell receptor signaling pathways were also dysregulated in cancer stem cells. The authors concluded that their findings demonstrate that global gene expression analysis combined "with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells."

Duke University Medical Center's scientists, T-A Read et al., published their study results in the February 3rd issue of Cancer Cell the identification of new marker for cancer stem cells. The investigators found that in contrary to human brain tumors in which the cells expressed the stem cell marker, CD133, that in a mouse medulloblastoma model, the tumor-propagating cells (TPCs)/cancer stem cells were not CD133+. The Patched mutant mouse had brain tumors with cells expressing the progenitor markers Math1 and CD15/SSEA-1. These cells were found to have increased proliferative capacity, greater resistance to apoptosis, and the ability to self-renew. The investigators noted that in a subset of human patients diagnosed with medulloblastomas, the tumors contained cells with gene expression profiles that were similar to the murine CD15+ cells. These subset of patients were noted to have a poorer prognosis. The authors concluded that their experimental results suggest that "CD15 may represent an important marker for TPCs in medulloblastoma."

Stanford University's scientists, T.C. P. Somervaille et al. published their findings in today's (Feb. 6th) issue of Cells Stem Cells on the genetic programs which maintain leukemic stem cells (LSCs) in the self-renewing state. In a mouse model of human acute myeloid leukemia (ALL), the investigators discovered a transcriptional subprogram of LSCs similar to that of embryonic stem cells for maintaining the cells in a self-renewing state. The program consisted of regulatory factors Myb, Hmgb3, and Cbx5 and, when co-expressed, the self-renewing state of the LSCs are maintained. The researchers also noted that expression of the transcription/chromatin regulatory factors in LSCs can result in leukemia-initiating stem cells that is independent of the MLLHoxa/Meis program (which is known to immortalize myeloid progenitors). The authors concluded that enhance expression of these self-renewing and ESC-like genes in normal myeloid progenitors can result in the conversion of these cells into malignant cancer stem cells and their enriched expression of the maintenance program in human malignancies can be linked to poor prognosis.