Project description:Chronic myelogenous leukemia (CML) is a malignant stem cell disease characterized by a reciprocal translocation between chromosome 9 and 22. The selective bcr-abl tyrosine-kinase inhibitor Imatinib has become the therapy of choice for patients with newly diagnosed CML including those previously considered candidates for allogeneic haematopoietic stem cell transplantation. The tyrosine-kinase inhibitor Nilotinib is a derivate of Imatinib with higher potency. To examine the molecular and functional effects of Nilotinib and Imatinib in chronic myelogenous leukemia, we performed gene expression and functional analyses in K562 cells following treatment with the two tyrosine kinase inhibitors. Experiment Overall Design: Affymetrix U133A 2.0 microarrays were used to examine the gene expression profile of K562 cells after in vitro treatment with Imatinib (0.5 µM) or Nilotinib (0.05 µM) for 24 hours. Gene expression data of the treated cells were compared with data of untreated cells.
Project description:In our previous study, the roles of heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) in CML cells were revealed. We found that overexpression of HNRPDL transformed murine BaF3 cells and induced lethal mice leukemia. Conversely, HNRPDL silencing inhibited colony-forming cell (CFC) production of CML CD34+ cells and attenuated BCR-ABL induced mice leukemia. In addition, HNRPDL modulated imatinib response of K562 cells and HNRPDL silencing sensitized CML CD34+ cells to imatinib treatment. To obtain molecular insights of how HNRPDL modulates the growth and imatinib response of human CML cells, we generated microarray data comparing HNRPDL silenced K562 cells with control (Scramble) cells.
