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CD133-Positive Hematopoietic Stem Cell "Stemness" Genes Contain Many Genes Mutated or Abnormally Expressed in Leukemia

^a Department of Pediatric Hemato-Oncology, Safra Children’s Hospital and
^b Department of Obstetrics and Gynecology, The Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;
^c Department of Molecular Cell Biology and
^d Department of Complex Systems, Weizmann Institute of Science, Rehovot, Israel;
^e Department of Obstetrics and Gynecology, Rambam Medical Center, Bruce Rappaport Institute of Technology, Technion-Israel Institute of Technology, Haifa, Israel

Key Words. Hematopoietic stem cells • Stemness • Peripheral blood • Cord blood • Gene expression

Correspondence: Amos Toren, M.D., Ph.D., Department of Pediatric Hematology-Oncology, Sheba Medical Center, Tel-Hashomer, Israel 52621. Telephone: 972-3-5303037; Fax: 972-3-5303031; e-mail: amost{at}post.tau.ac.il

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.

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