Cell Cycle Arrest of Jurkat Cells by Leukemic Bone Marrow Stromal Cells: Possible Mechanisms and Involvement of CRIF1

Abstract

Bone marrow hemopoietic microenvironment plays an important role in the incidence and development of leukemia. Studies using normal bone marrow stromal cells (BMSCs) and an established stromal cell line, have shown that the leukemic cell cycle can be arrested in the G0/G1 phase in BMSCs, although the mechanism is still unclear. We performed this study to determine the effect of primary cultured leukemic BMSCs on the cell cycle distribution of Jurkat cells. Normal and leukemic BMSCs were isolated for culture to create a hematopoietic microenvironment simulating bone marrow in vitro. The normal and leukemic BMSCs induced cell cycle arrest of Jurkat cells in the G0/G1 phase. Suppression subtractive hybridization revealed differential gene expression after the co-culture of cells with normal and leukemic BMSCs. Jurkat cells showed upregulated expression of genes involved in cell cycle control CR6 interacting factor 1 (CRIF1). Reverse transcriptase polymerase chain reaction results also showed increased CRIF1 mRNA levels in Jurkat cells co-cultured with either normal BMSCs or leukemic BMSCs compared with a suspension culture group: 5.16 ± 0.75, 6.13 ± 0.63 versus 3.02 ± 0.32, respectively ( P < .05). These results indicated cell cycle arrest of Jurkat cells in the G0/G1 phase to be induced by primary cultured leukemic BMSCs associated with increased expression of CRIF1 by leukemic cells.