Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia.

Autor: Čokić VP; Institute for Medical Research, University of Belgrade, Belgrade, Serbia. Electronic address: vl@imi.bg.ac.rs., Mojsilović S; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Jauković A; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Kraguljac-Kurtović N; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia., Mojsilović S; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Šefer D; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia., Mitrović Ajtić O; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Milošević V; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia., Bogdanović A; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia., Đikić D; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Milenković P; Institute for Medical Research, University of Belgrade, Belgrade, Serbia., Puri RK; Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: Blood cells, molecules & diseases [Blood Cells Mol Dis] 2015 Dec; Vol. 55 (4), pp. 373-81. Date of Electronic Publication: 2015 Aug 07.
DOI: 10.1016/j.bcmd.2015.08.002
Abstrakt: Purpose: 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.
Conclusion: 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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