reciprocal t(9;22) ablbcr fusion proteins leukemogenic potential and effects on b cell commitment互惠的t(9、22)ablbcr融合蛋白引起白血病的潜力和影响b细胞的承诺.pdfVIP

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reciprocal t(9;22) ablbcr fusion proteins leukemogenic potential and effects on b cell commitment互惠的t(9、22)ablbcr融合蛋白引起白血病的潜力和影响b细胞的承诺.pdf

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reciprocal t(9;22) ablbcr fusion proteins leukemogenic potential and effects on b cell commitment互惠的t(9、22)ablbcr融合蛋白引起白血病的潜力和影响b细胞的承诺

Reciprocal t(9;22) ABL/BCR Fusion Proteins: Leukemogenic Potential and Effects on B Cell Commitment 1,2 1 3 2 1 Xiaomin Zheng , Claudia Oancea , Reinhard Henschler , Malcolm A. S. Moore , Martin Ruthardt * 1 Department of Hematology, Laboratory for Tumor Stem Cell Biology, Goethe University, Frankfurt, Germany, 2 Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 3 Department of Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany Abstract + Background: t(9;22) is a balanced translocation, and the chromosome 22 breakpoints (Philadelphia chromosome – Ph ) determine formation of different fusion genes that are associated with either Ph+ acute lymphatic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML). The ‘‘minor’’ breakpoint in Ph+ ALL encodes p185BCR/ABL from der22 and p96ABL/BCR from der9. The ‘‘major’’ breakpoint in CML encodes p210BCR/ABL and p40ABL/BCR . Herein, we investigated the leukemogenic potential of the der9-associated p96ABL/BCR and p40ABL/BCR fusion proteins and their roles in the lineage commitment of hematopoietic stem cells in comparison to BCR/ABL. Methodology: All t(9;22) derived proteins were retrovirally expressed in murine hematopoietic stem cells (SL cells) and human umbilical cord blood cells (UCBC). Stem cell potential was determined by replating efficiency, colony forming - spleen and competitive repopulating assays. The leukemic potential of the ABL/BCR fusion prot