Clinical and laboratory studies of expression of cyclin A in leukemia cells.
Uncontrolled cell proliferation is the basic feature of cancer. Some of the prime cell cycle regulators are involved directly in tumorigenesis. Cyclin A, one of the G(1)/S cyclin, can cause transformation. The purpose of this research was to investigate whether cyclin A overexpression was involved in leukemogenesis and proliferation of leukemia cells. The expression of cyclin A at S-phase in leukemia cell line HL-60, blast cells of acute leukemia patients, bone marrow cells of outpatients without malignant hematological disease and peripheral blood cells of healthy donors was investigated by simultaneous indirect immunofluorescence staining of intracellular antigen and DNA. To further investigate whether cyclin A played as a key molecular in cell proliferation, HL-60 cells were exposed to different concentrations of hexamethylene bisacetamide (HMBA). MTT dye absorbance of living cells and cell cycle analysis were adopted to evaluate growth arrest. Differentiation was evaluated by detection of the change of expression of CD11b and CD33 on cell surface. The results showed that overexpression of cyclin A was only found among specimens from acute leukemia and leukemia cell line. There was no elevated cyclin A detection for cyclin A among specimens from outpatients and healthy donors. In HMBA interference experiment, HMBA was able to induce growth arrest and monocytic macrophage differentiation of HL-60 cells in a dose-dependent manner, and all these changes were associated with a marked down-regulation of cyclin A expression. In conclusion, aberrant overexpression of cyclin A at S-phase was only found in leukemia cell lines and blast cells from acute leukemia. The dose-dependent effect of HMBA on cell growth and differentiation of HL-60 cell line which was consistent with the decrease of cyclin A expression in these cells suggested that the molecular mechanisms of HMBA inducement involved downregulation of cyclin A expression.
Department of Hematology, Huashan Hospital, Medical School of Fudan University, Shanghai 200040, China. qlfs@sh163.net
Hui
H
Yu
Yan-Hui
YH
Xie
Hua-Hua
HH
Fan
Bin
B
Zheng
Yi
Y
Xie
D000081:Acetamides / Q000494:pharmacology; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019925:Cyclin A / Q000032:analysis* / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D000081:Acetamides; D019925:Cyclin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C014026:hexamethylene bisacetamide