Abstract
Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells using the reprogramming factors (Oct4, Sox2, Klf4 and c-Myc, also called OSKM).1 Cellular reprogramming and oncogenesis share many common features. The application of the iPS technology in cancers help us better understand the mechanism underlying the initiation and progression of cancer. Therefore, defining the reprogramming potential of cancer cells would provide unique opportunities to reveal epigenetic mechanisms and develop novel therapeutics for cancer. Because the reprogramming efficiency of cancer cells is paradoxically much lower than that of normal cells in general, only some handful types of cancer cells have been explored using the iPS technology.2 To date, in the hematopoietic system, Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines, human chronic myeloid leukemia cells, juvenile myelomonocytic leukemia cells and primary murine mixed lineage leukemia-AF9 acute myeloid leukemia cells have been successfully generated into iPS cells.3, 4, 5, 6 However, whether the primary malignant leukemic T cells can be reprogrammed into the iPS cells is still a mystery.
Highlights
Somatic cells can be reprogrammed into induced pluripotent stem cells using the reprogramming factors (Oct[4], Sox[2], Klf[4] and c-Myc, called OSKM).[1]
In the hematopoietic system, Epstein-Barr virus (EBV)transformed lymphoblastoid cell lines, human chronic myeloid leukemia cells, juvenile myelomonocytic leukemia cells and primary murine mixed lineage leukemia-AF9 acute myeloid leukemia cells have been successfully generated into induced pluripotent stem (iPS) cells.[3,4,5,6]
green fluorescent protein (GFP) was not expressed in the established leukemia iPS (L-iPS) cells (Figure 1d), indicating that the retroviral vector was silenced in L-iPS cells
Summary
Blood Cancer Journal (2016) 6, e444; doi:10.1038/bcj.2016.57; published online 8 July 2016. The retroviral-expressed Notch[1] in certain leukemia cells was not sufficient to silence This may explain at least in part why the GFP+ colonies could not be fully reprogrammed into iPS cells. The gene expression profile of GFP− colonies was much more similar to L-iPS cells than the GFP+ colonies (Supplementary Figure S3A). The gene expression trend showed that the expression of pluripotency genes, such as Nanog, Sox[2], Oct[4] and Sall[4], were continuously increased from the leukemia cells to the L-iPS cells (Supplementary Figure S3B). The gene expression differences between GFP+ and GFP− colonies may provide insights into the potential barriers for reprogramming of T-ALL cells. Our results indicate that the inhibition of apoptosis, NF-κB, DOT1L and LSD1 can increase the reprogramming efficiency of T-ALL cells. Our study demonstrated that the primary mouse T-ALL cells can be fully
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