Japanese scientists, Y. Aikawa et al., from the National Cancer Center Research Institute (Tsukiji) reported in a letter in the April 25th online edition of Nature Medicine their findings identifying a subpopulation of cancer stem cells in mouse model for acute myeloid leukemia (AML). The investigators found that cells expressing high levels of the receptor for marcophage colony simulating factor (CSF1R) had potent leukemia-initiating activity. With a leukemia-associated monocytic leukemia zinc finger fusion protein (MOZ)-TIF2, the fusion protein interacts with the PU.1 promoter and subsequent induction in high CSF1R expression. The investigators also found that cells expressing high levels of CSF1R were subpopulation of cancer stem cells which were essential for maintaining AML. In transgenic mice expressing the drug inducible suicide gene controlled by the CSF-1R promoter, the researchers were able to cure the AML in the presence of the drug; which suggests ablation of the AML stem cells. Moreover, induction of AML was suppressed in CSF1R-deficient mice as well as in mice treated with inhibitors to CSF1R. The authors concluded from their observation that targeting PU.1-mediated upregulation of CSF1R expression might be a useful therapeutic approach."

In a study published in the April 19th online edition of PNAS, K. M. Dhodapkar et al. from Yale University investigated natural immunity to the Oct4 transcription factor, whose expression is critical for pluripotency in human embryonic stem cells as well as induced pluripotent stem cells (iPSCs). In healthy human subjects, freshly isolated T cells were found to have specificity to Oct4 in over 80% of the healthy donors. The reactive Tcells were predominantly CD4+ T cells residing in the CD45RO+ T cell memory compartment. Proliferative T cell responses were induced when the cells had been exposed to dendritic cells which were pulsed with Oct4-derived peptides. Additionally, the researchers found that in cancer patients diagnosed with germ-cell tumors, such as testicular cancer, 35% of the patients had T cells with specificity to the Oct4 antigen. However, the investigators found that following chemotherapy of the germ-cell tumors, there was apparently an "induction of anti-Oct4 immunity in vivo in patients lacking such responses." The authors concluded that study results suggest that there is a "surprising lack of immune tolerance to this crticial pluripotency antigen in humans...and "harnessing natural immunity to this antigen may allow immune-based targeting of pluripotency-related pathways for prevention of cancers, including those in the setting of ES/IPS-based therapies."

In the April 16th online edition of Stem Cells, K. E. Hovinga et al. from Memorial Sloan-Kettering Cancer Center (New York) reported their experimental findings on anlayzing cancer stem cells derived from patients with glioblastoma multiforme (GBM). With a three-dimensional organotypic cultures derived from explants of GBM patients, the investigators found that Notch inhibition in the explants resulted in decreased proliferation of tumor cells concomitant with a decrease in endotlthelial cells. Additionally, selective elimination of the endolthelial cells with a specific cytotoxic reagent resulted in a decrease in self-renewing cancer stem cells. The researchers concluded that this particular observation suggests the endolthelial cells in the tumor have a critical role for cancer stem cell maintenance in GBM which is partly mediated by Notch signaling. With neurosphere derived from CD133+ cells, the researchers exposed both the neurospheres and explants to radiation and in combination with Notch signaling blockade. Radiation and Notch blockade resulted in a substantial decrease in self-renewal in tumor explants and in neurospheres, whereas radiation alone was less effective on the explant. The authors concluded that the "Notch signaling pathway plays a critical role in linking angiogenesis and cancer stem cells self-renewal and is thus a potential therapeutic target."

In the April 1st issue of Genes & Development, H-K Liu et al. from Dusseldorf University reported their study results dissecting the molecular pathogenesis of gliomablastoma in a mouse model. The investigators found that neural stem cells (NSCs) residing in the subventricular zone (SVZ) of the brain can give rise to glioma-like lesion and gliomas, if they overexpress the nuclear receptor tailless (Tlx). The researchers noted that Tlx is a major regulator of NSC expansion. However, overexpression of Tlx in NSCs can result in migration of neural stem/progenitor cells from their natural niche which can result in gliomagenesis. Additionally, the experimental results demonstrated that glioma development is accelerated with overexpression of Tlx and loss of p53 activity. It appears Tlx-induce NSC expansion results in increased angiogenesis concomitant with migration of the glioma cells to a perivascular niche. Cells residing in this niche were also found to be nestin positive perivascular malignant cells. The authors concluded that their study "demonstrates how NSCs contribute to brain tumorgenesis driven by a stem cell-specific transcription factor, thus providing novel insights into the histogenesis and molecular pathogenesis of primary brain tumors."