CD133‐Positive Hematopoietic Stem Cell “Stemness” Genes Contain Many Genes Mutated or Abnormally Expressed in Leukemia

Abstract

Affymetrix human Hu133A oligonucleotide arrays were used to study the expression profile of CD133 + cord blood (CB) and peripheral blood (PB) using CD133 cell-surface marker. An unsupervised hierarchical clustering of 14,025 valid probe sets showed a clear distinction between the CD133 + cells representing the hematopoietic stem cell (HSC) population and CD133-differentiated cells. Two hundred forty-four genes were found to be upregulated by at least twofold in the CD133-positive cells of both CB and PB compared with the CD133-negative cells. These genes represent the hematopoietic "stemness," whereas the 218 and 304 upregulated genes exclusively in PB and CB, respectively, represent tissue specificity. Some of the stemness genes were also common to HSC genes found to be upregulated in several recently published studies. Among these common stemness genes, we identified several groups of genes that have an important role in hematopoiesis: growth factor receptors, transcription factors, genes that have an important role in development, and genes involved in cell growth. Sixteen selected stemness genes 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 upon mutation or change of their expression. Stem Cells

The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence

“…Low expression of CD133 glycoprotein is associated with a more mature, proliferative cell fraction. 35 We also found a decreased expression of the genes encoding for L-selectin and CD53 in the HSC subset of CML patients (Table 1). These molecules seem to segregate asymmetrically in HSC according to the model of asymmetric cell division and characterize daughter cells that maintain stem-cell fate.…”

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE

“…Recently, oligonucleotide microarrays were used for the gene expression profiling of untreated CD133 + HSCs (CD133 + vs CD133 -) [33,34]. Both studies used the same Figure 6 Comparison mapping of genes expressed in erythroid and myeloid development and differentiation to biological processes.…”

“…npg procedures for enrichment of CD133 + cells, purification of RNA, amplification and labeling of RNA probes, and almost the same oligonucleotide microarrays (HG-U133A from Affymetrix), GeneChip scanners, and GeneChip operating software for data analyses. One study identified 690 differentially expressed genes and another identified 584 differentially expressed genes; however, some were inconsistent between these two studies [33,34]. Here, we analyzed the expression patterns of gene, protein and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of CD133 + HSCs in response to EPO and G-CSF.…”

Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia

“…For example, it occurred at the PROM1 (prominin-1/CD133) gene (Fig. 1B), which encodes a defining antigen of hematopoietic stem cells and is purported to play a role in asymmetric cell divisions in adult stem cells (Wagner et al 2004;Toren et al 2005), and HOXA7, HOXA9, HOXA10 ( Fig. 2A), whose overexpression are hallmarks of ALLs carrying the t(4;11) chromosome translocation (Rozovskaia et al 2001(Rozovskaia et al , 2003Armstrong et al 2002;Yeoh et al 2002;Ferrando et al 2003).…”