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

PurposeWe 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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.