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Acta Haematol. 2019 May 21:1-9. doi: 10.1159/000495456. [Epub ahead of print]

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.

Author information

1
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
2
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
3
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, mkonople@mdanderson.org.
6
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, mkonople@mdanderson.org.

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.

KEYWORDS:

Acute myeloid leukemia; Allogeneic stem cell transplantation; CXCR4; Plerixafor; Proteomic profiling of signaling

PMID:
31112940
DOI:
10.1159/000495456

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