Čokić Vladan P, Mojsilović Slavko, Jauković Aleksandra, Kraguljac-Kurtović Nada, Mojsilović Sonja, Šefer Dijana, Mitrović Ajtić Olivera, Milošević Violeta, Bogdanović Andrija, Đikić Dragoslava, Milenković Pavle, Puri Raj K
Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
Blood Cells Mol Dis. 2015 Dec;55(4):373-81. doi: 10.1016/j.bcmd.2015.08.002. Epub 2015 Aug 7.
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.
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.
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.
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.
我们比较了慢性髓性白血病（CML）患者外周血CD34(+)细胞和粒细胞的基因表达谱，重点关注受BCR-ABL癌基因影响的信号通路。
对7例CML患者和7名健康供者外周血中的循环CD34(+)细胞和粒细胞进行了微阵列分析。所有研究的BCR-ABL阳性CML患者均处于慢性期，外周血中CD34(+)细胞的平均值为2012±标准差/μl。
与粒细胞（2701个基因）相比，CML CD34(+)细胞中的基因表达谱更为显著（3553个基因）。分别有41个和39个基因在CML CD34(+)细胞（HINT1、TXN、SERBP1）和粒细胞中显著上调。BCR-ABL癌基因通过显著上调PTPN11、CDK4/6和MYC以及降低CD34(+)细胞中E2F1、KRAS和NFKBIA基因的表达来激活PI3K/AKT和MAPK信号通路。在与BCR-ABL抑制剂伊马替尼抑制细胞增殖相关的基因中，FOS和STAT1在CML中表达显著降低。
BCR-ABL融合基因的存在使参与CD34(+)细胞周期调控、增殖和凋亡的基因表达量增加了一倍。这些结果确定了CML患者PI3K/AKT和MAPK信号通路中的修饰基因。
