Proteomic Profiling of Signaling Networks Modulated by G-CSF/Plerixafor/Busulfan-Fludarabine Conditioning in Acute Myeloid Leukemia Patients in Remission or with Active Disease prior to Allogeneic Stem Cell Transplantation

异基因干细胞移植前处于缓解期或活动性疾病的急性髓系白血病患者接受 G-CSF/普乐沙福/白消安-氟达拉滨治疗后信号网络的蛋白质组学分析

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作者:Zhihong Zeng, Wenbin Liu, Christopher B Benton, Sergej Konoplev, Hongbo Lu, Rui-Yu Wang, Julianne Chen, Elizabeth Shpall, Keith A Baggerly, Richard Champlin, Marina Konopleva

Abstract

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.

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