4.2 Article

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

Journal

ACTA HAEMATOLOGICA
Volume 142, Issue 3, Pages 176-184

Publisher

KARGER
DOI: 10.1159/000495456

Keywords

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

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Funding

  1. National Institutes of Health/National Cancer Institute (NIH/NCI) [R21 CA137637]
  2. Leukemia and Lymphoma Society [6427-13]
  3. NIH/NCI Cancer Center [P30 CA016672]

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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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