Journal
ACTA HAEMATOLOGICA
Volume 142, Issue 3, Pages 176-184Publisher
KARGER
DOI: 10.1159/000495456
Keywords
Acute myeloid leukemia; CXCR4; Proteomic profiling of signaling; Plerixafor; Allogeneic stem cell transplantation
Categories
Funding
- National Institutes of Health/National Cancer Institute (NIH/NCI) [R21 CA137637]
- Leukemia and Lymphoma Society [6427-13]
- 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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