ABSTRACT
In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
ABSTRACT
In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
ABSTRACT
OBJECTIVE: To investigated influence of co-stimulatory signal produced by CD40/CD40 ligand (CD40L) on proliferation and differentiation of leukemic stem cells and B cells as well as the role of CD40L anti-leukemia.DATA SOURCES: We searched Pubmed database and Springer database for the related literatures on CD40/40L, leukemic stem cell and leukemia published from January 1995 to December 2005, using the keyword "CD40, 40L, leukemic stem cell, leukemia" in English.STUDY SELECTION: We focused on published data that included the literatures of experimental groups and control groups, excluded obviously no random experiments, no random clinical studies and repeated researches.DATA EXTRACTION: We collected 30 experimental articles on influence of co-stimulatory signal produced by CD40/CD40L on proliferation and differentiation of leukemic stem cells and B cells as well as the role of CD40L anti-leukemia. Twenty-three articles that met inclusion criteria, excluded 7 articles were the same research ones.DATA SYNTHESIS: Twenty-three trials included influence of co-stimulatory signal produced by CD40/CD40L on proliferation and differentiation of leukemic stem cells, B cells and prognosis of leukemia, and the treatment of leukemic patients by CD40L. We analyzed the influence and role of co-stimulatory signal produced by CD40/CD40L on proliferation and differentiation of leukemic stem cells, B cells and leukemia.CONCLUSION: The evidence conformed that co-stimulatory signal produced by CD40/CD40L promoted proliferation and differentiation of leukemic stem cells , B cells, and it is important for the occurrence,progress and prognosis of leukemia. CD40/CD40L plays a crucial part in immune response, and proves wide application in the immune therapy of leukemia.