title: Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia.
abstract: OBJECTIVE
  We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene.
  
  
  METHODS
  The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34(+)cells/μl in peripheral blood.
  
  
  RESULTS
  The gene expression profile was more prominent in CML CD34(+) cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34(+) cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34(+) cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML.
  
  
  CONCLUSIONS
  The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34(+) cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects.
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia. Electronic address: vl@imi.bg.ac.rs.
authors.forename: Vladan P
authors.initials: VP
authors.lastname: Čokić
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jauković
authors.affiliation: Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Kraguljac-Kurtović
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Šefer
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Olivera
authors.initials: O
authors.lastname: Mitrović Ajtić
authors.affiliation: Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Violeta
authors.initials: V
authors.lastname: Milošević
authors.affiliation: Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Andrija
authors.initials: A
authors.lastname: Bogdanović
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragoslava
authors.initials: D
authors.lastname: Đikić
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Pavle
authors.initials: P
authors.lastname: Milenković
authors.affiliation: Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006098:Granulocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016044:Fusion Proteins, bcr-abl
keywords: CD34(+) cells; Chronic myeloid leukemia; Granulocytes; Microarray analysis