[Study on gene expression of TGF beta 1 and its receptor in leukemia cells and the serum TGF beta 1 level in the patients with acute leukemia].

OBJECTIVE

To investigate the mechanism by which TGF beta 1 inhibits the growth of leukemic cells and the significance of serum TGF beta 1 level in acute leukemia(AL) patients.

METHODS

RT-PCR was used to detect gene expression of cytokines including IL-1, IL-3, IL-6, TGF beta 1 and their receptors (R) in leukemic and normal cells. Leukemic colony assay was carried out to determine the effect of TGF beta 1 on the growth of leukemic cells and the serum TGF beta 1 level in 33 AL patients were measured by ELISA.

RESULTS

TGF beta 1 was found to significantly inhibit the proliferation of leukemia cells of HL-60, K562 and DAMI cell lines. Furthermore, a variety of leukemia cell lines including HEL, HL-60, K562, U937, DAMI, MEG-01, HUT78 and CA were found to express mRNAs for TGF beta 1 and its receptor. In addition, TGF beta 1 was found to be able to evidently down-regulate the expression of mRNAs for IL-6, IL-6R, IL-3, GM-CSFR in DAMI cells and, interestingly, up-regulate TGF beta 1 gene expression in the cells per se before the cells showed DNA fragmentation, a molecular hallmark for cell apoptosis. It was shown that serum TGF beta 1 levels were significantly decreased in leukemic patients, restored to normal in the patients achieved complete remission, and tended to decrease again in the recurrent patients.

CONCLUSION

1. TGF beta 1 may act as an inhibitory autocrine factor in the proliferation of leukemia cells; 2. the mechanism by which TGF beta 1 inhibits the growth of leukemia cells involves its down-regulating expression of positive cytokines and receptors and up-regulating TGF beta 1 expression in leukemia cells per se; 3. serum TGF beta 1 is a valuable parameter in monitoring the prognosis of leukemia and weakened control of TGF beta 1 on leukemia cells may play an important role in the pathogenesis of AL.