Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Acta Haematol. 2019;142(3):176-184. doi: 10.1159/000495456. Epub 2019 May 21.
To characterize intracellular signaling in peripheral blood (PB) cells of acute myeloid leukemia (AML) patients undergoing pretransplant conditioning with CXCR4 inhibitor plerixafor, granulocyte colony-stimulating factor (G-CSF), and busulfan plus fludarabine (Bu+Flu) chemotherapy, we profiled 153 proteins in 33 functional groups using reverse phase protein array. CXCR4 inhibition mobilized AML progenitors and clonal AML cells, and this was associated with molecular markers of cell cycle progression. G-CSF/plerixafor and G-CSF/plerixafor/Bu+Flu modulated distinct signaling networks in AML blasts of patients undergoing conditioning with active disease compared to nonleukemic PB cells of patients in remission. We identified AML-specific proteins that remained aberrantly expressed after chemotherapy, representing putative chemoresistance markers in AML.
为了描述接受 CXCR4 抑制剂plerixafor、粒细胞集落刺激因子（G-CSF）和白消安联合氟达拉滨（Bu+Flu）化疗预处理的急性髓系白血病（AML）患者外周血（PB）细胞内的信号转导，我们使用反相蛋白阵列对 33 个功能组的 153 种蛋白质进行了分析。CXCR4 抑制可动员 AML 祖细胞和克隆性 AML 细胞，这与细胞周期进程的分子标志物相关。与缓解期患者的非白血病 PB 细胞相比，G-CSF/plerixafor 和 G-CSF/plerixafor/Bu+Flu 在接受有活性疾病预处理的患者的 AML 原始细胞中调节了不同的信号转导网络。我们鉴定了在化疗后仍异常表达的 AML 特异性蛋白，这些蛋白可能是 AML 的潜在耐药性标志物。
