Transcriptome analysis of PBX1 silenced chronic myeloid leukemia CD34+ cells

• 1、Cyrus Tang Hematology Center, Soochow University, Suzhou 215123

Abstract：Objective: The present study aims to understand the molecular mechanism of how PBX1 silencing inhibits the growth of chronic myeloid leukemia (CML) cells. Methods: The control and PBX1 silenced K562 cells were subjected to apoptosis analysis with 7-AAD/Annexin V staining, with and without imatinib mesylate (IM) treatment. The colony-forming cell (CFC) production of control and PBX1 silenced human normal bone marrow CD34+ cells was measured. RNA-seq data of control and PBX1 silenced CML CD34+ cells were obtained, and gene expression validation with various cellular models was performed. Results: Silence of PBX1 increased apoptotic index of K562 cells without IM treatment, and PBX silencing promoted apoptosis of K562 cells induced by IM treatment. PBX1 silencing inhibited the CFC production of normal CD34+ cells, suggesting an improtant role of PBX1 in regulating human normal hematopoesis. The expression of several transcripts, including UCHL3, FUT8, MAPKAP1 and KDM1B were significantly inhibited upon PBX1 silencing, and these transcripts had higher expression in CML CD34+ cells than normal control cells, suggesting possible roles of these candidate genes in CML pathology. Conclusion: PBX1 silencing increased the apoptotic index of K562 cells, and rendered these cells enhanced response to IM induced apoptosis. PBX1 silencing inhibited the CFC production of normal CD34+ cells, suggesting an improtant role of PBX1 in regulating normal hematopoesis. RNA-seq data and following validation with several cellular models provided pivotal clues to delineate PBX1 silecing mediated inhibition of CML CD34+ cells.

Keywords： chronic myeloid leukemia PBX1 CD34+ cells