The cell analysis and FACS Core facility provides genotypic and phenotypic analysis and separated cell populations to the investigators of this program. The laboratory has provided and developed cutting edge techniques in single cell analysis. For the quantitation of apoptotic cells, the Tdt- b-dUTP assay (TUNEL) was established and modified for multi-parameter analysis in combination with DNA and BUdR measurements (cell cycle ploidy). Also, immunophenotypic analysis of progenitor cells and lineage restricted cell populations, analysis of intracellular proteins related to apoptosis (bcl-2, bax, p53), and of cell surface antigens including fas and MDR1 is provided. Recently, binding of Annexin V to phosphatidyl serine (PS) was recognized as a test for changes in the membrane lipid structure that precedes changes detected by TUNEL in cells initiating apoptosis. Quantitation of cellular antigens allows us to determine the Antibody Binding Capacity (ABC). Retrovirally-transduced cells will be analyzed for expression of transgene (NGF receptor) and FACS-sorted CD34 cells will be separated for subsequent analysis by MACS, and CD34 subpopulations by MACS/FACS. Cell kinetic changes can be studied in vitro and the number of actual cell divisions can be determined using PKH26, with cells undergoing none or up to ten divisions being separated for subsequent molecular analysis. Fluorescence in situ hybridization (FISH) to determine the number of t(9,22) containing interphase cells has been established. The combination of FISH and TUNEL or PS/Annexin V assays allows us to discriminate apoptosis in normal and leukemic cells. A novel assay has been developed to determine bcr-abl transcripts in situ by RT- PCR. This assay will be compared to hypermetaphase FISH and competitive RT-PCR for the detection of low levels of residual leukemic cells. Finally, progenitor cell compartments (CD34 and """"""""SP"""""""" cells) will be analyzed for the presence of Ph cells, based on our observation that normal but not CML cells express MDR1 and that fas (CD95) is expressed more in CML than in normal progenitor cells.

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Alhuraiji, Ahmad; Kantarjian, Hagop; Boddu, Prajwal et al. (2018) Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. Am J Hematol 93:84-90
Ishizawa, Jo; Nakamaru, Kenji; Seki, Takahiko et al. (2018) Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition. Cancer Res 78:2721-2731
Boddu, Prajwal; Benton, Christopher B; Wang, Wei et al. (2018) Erythroleukemia-historical perspectives and recent advances in diagnosis and management. Blood Rev 32:96-105
Ruvolo, Peter P; Ruvolo, Vivian R; Burks, Jared K et al. (2018) Role of MSC-derived galectin 3 in the AML microenvironment. Biochim Biophys Acta Mol Cell Res 1865:959-969
Cortes, Jorge E; Gambacorti-Passerini, Carlo; Deininger, Michael W et al. (2018) Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol 36:231-237
Sasaki, Koji; Kantarjian, Hagop; O'Brien, Susan et al. (2018) Prediction for sustained deep molecular response of BCR-ABL1 levels in patients with chronic myeloid leukemia in chronic phase. Cancer 124:1160-1168
Gambacorti-Passerini, Carlo; Cortes, Jorge E; Lipton, Jeff H et al. (2018) Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica 103:1298-1307
Boddu, Prajwal; Shah, Abdul Rashid; Borthakur, Gautam et al. (2018) Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting. Leuk Lymphoma 59:1312-1322
Kornblau, Steven M; Ruvolo, Peter P; Wang, Rui-Yu et al. (2018) Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival. Haematologica 103:810-821
Zhang, Weiguo; Ly, Charlie; Ishizawa, Jo et al. (2018) Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis in FLT3-mutated acute myeloid leukemias: from concept to clinical trial. Haematologica 103:1642-1653

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