CD133-positive hematopoietic stem cells “stemness” genes contain many genes mutated or abnormally expressed in leukemia (2005)

Several groups have recently used microarray technology to study the common characteristics of stem cells from different tissues (“stemness”) and the typical features of stem cells from various sources (“tissue specificity”). Most groups focused their study on mice, used relatively small cDNA microarrays, and used CD34 as the cell surface marker for hematopoietic stem cells isolation. We studied HSC cells from cord blood (CB) and peripheral blood (PB)characterized by expression of the primitive CD133 antigen, and used the Affymetrix Human Hu133A oligonucleotide arrays to study the gene expression profile of these cells.An unsupervised hierarchical clustering of 14,025 “valid” probe sets showed a clear distinction between the CD133+ cells representing the stem cell population and CD133− cells that represent various stages of cell differentiation. Comparison of CD133+ cells isolated from CB and PB to CD133− cells identified 304 genes that were up-regulated by at least 2-fold in CB and 218 genes in PB. These genes were considered source-specific and possibly relevant to the unique properties of CB- and PB-derived HSC. A total of 244 genes were found to be up-regulated by at least 2-fold in the CD133+ cells of both CB and PB compared with the CD133− cells. Comparison of these “stemness” genes to the lists of “stemness” genes that were identified by 2 recent studies that analyzed mainly murine HSC identified totals of 33 and 65 common genes. Twenty-four genes were common to another study that analyzed human HSC.Among these common “stemness” genes, we identified several groups of genes that have an important role in hematopoiesis: growth factor receptors, a group of transcription factors that includes several homeobox genes and TGF-β target genes, genes that have an important role in development, and genes involved in cell growth. Among these 4 groups, we identified 16 “stemness” genes (MPL, FLT3, HOXA9, MEIS 1, MLLT3, KIT, TIE, GATA-2, HOXA5, HOXA10, HLF, MYCN, EVI1, MYB, FHL1, and HMGA2) that are known to be mutated or abnormally regulated in acute leukemias. It can be suggested that key hematopoietic stemness machinery genes may lead to abnormal proliferation and leukemia on mutation or change of expression. Several groups have recently used microarray technology to study the common characteristics of stem cells from different tissues (“stemness”) and the typical features of stem cells from various sources (“tissue specificity”). Most groups focused their study on mice, used relatively small cDNA microarrays, and used CD34 as the cell surface marker for hematopoietic stem cells isolation. We studied HSC cells from cord blood (CB) and peripheral blood (PB)characterized by expression of the primitive CD133 antigen, and used the Affymetrix Human Hu133A oligonucleotide arrays to study the gene expression profile of these cells. An unsupervised hierarchical clustering of 14,025 “valid” probe sets showed a clear distinction between the CD133+ cells representing the stem cell population and CD133− cells that represent various stages of cell differentiation. Comparison of CD133+ cells isolated from CB and PB to CD133− cells identified 304 genes that were up-regulated by at least 2-fold in CB and 218 genes in PB. These genes were considered source-specific and possibly relevant to the unique properties of CB- and PB-derived HSC. A total of 244 genes were found to be up-regulated by at least 2-fold in the CD133+ cells of both CB and PB compared with the CD133− cells. Comparison of these “stemness” genes to the lists of “stemness” genes that were identified by 2 recent studies that analyzed mainly murine HSC identified totals of 33 and 65 common genes. Twenty-four genes were common to another study that analyzed human HSC. Among these common “stemness” genes, we identified several groups of genes that have an important role in hematopoiesis: growth factor receptors, a group of transcription factors that includes several homeobox genes and TGF-β target genes, genes that have an important role in development, and genes involved in cell growth. Among these 4 groups, we identified 16 “stemness” genes (MPL, FLT3, HOXA9, MEIS 1, MLLT3, KIT, TIE, GATA-2, HOXA5, HOXA10, HLF, MYCN, EVI1, MYB, FHL1, and HMGA2) that are known to be mutated or abnormally regulated in acute leukemias. It can be suggested that key hematopoietic stemness machinery genes may lead to abnormal proliferation and leukemia on mutation or change of expression.