Changes And Clinical Significances Of Expressions Of CD4~+T Cell Subsets Transcription Factors In Patients With AA, MDS And AML

OBJECTIVE This study was aimed to compare the expressions of specific transcription factors of T-bet, GATA-3, RORyt and Foxp3mRNA in peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML), and investigate their immune status and pathogenesis, so as to provide experimental basis for the choice of clinical treatment.METHODS During the time between July2012and July2013, collected the Peripheral Blood Mononuclear Cells (PBMCs) from82patients from the Department of Hematology, Provincial Hospital affiliated to Shandong Uneiversity. The mRNA expression of T-box (T-bet), GATA-3, ROR-yt and Foxp3in PBMCs were examined by RT-PCR, in42cases of MDS, including22refractory anemia(MDS-RA),20refractory anemia with excess blasts(MDS-RAEB),23AA,17AML patients and16healthy volunteers respectively..RESULTS1. Changes of mRNA Expression Levels of transcription factors in patients and controls.The data was presented as the fold change in gene expression normalised to an endogenous reference gene and relative to healthy controls. Compared with normal control group, the relative levels of the mRNA gene expression of T-bet, RORyt in AA group patients were significantly higher (p<0.01), while the mRNA levels of GATA3and Foxp3were lower (p<0.01). There were no significant difference in expression of T-bet and GATA3between MDS group and normal control group, but the expression levels of Foxp3and RORyt were higher than those in normal controls (p<0.05); T-bet and RORyt in MDS-RA group were higher than those in the controls (p<0.01), but the GATA3expression significantly was reduced (p<0.05), however, there was no significant difference in expression of Foxp3between MDS-RA and the controls. Expressions of T-bet and RORyt in patients with MDS-RAEB and AML were lower than those of normal controls (p<0.05), but the expression levels of GATA3and Foxp3mRNA were significantly higher (p<0.01).2. Changes of mRNA Expression Levels of transcription factors in AA and MDS.Compared with the AA group, the results showed no statistically significant differences in T-bet, and RORyt from those of MDS-RA, while the relative mRNA expression levels of GATA3and Foxp3were increased (p<0.05).While the expression levels of T-bet and RORyt in MDS-RAEB group were lower (p<0.05), the MDS-RAEB patients showed a significant increase in the levels of GATA3and Foxp3(p<0.05).3. Changes of mRNA Expression Levels of transcription factors in MDS-RA and MDS-RAEB.Compared with the MDS-RA group, the expression levels of T-bet and RORyt in MDS-RAEB group were lower (p<0.05), while the MDS-RAEB patients showed a significant increase in the levels of GATA3and Foxp3(p<0.05).4. Changes of mRNA Expression Levels of transcription factors in MDS and AML.Compared with MDS-RAEB, the expression levels of T-bet showed decreased in AML patients (p<0.05), while the mRNA expression levels of GATA3and Foxp3were increased (p<0.05), as well as no significant difference in RORyt expression was found between MDS-RAEB and AML.CONCLUSIONS1. The upregulation of T-bet, RORyt in AA patients resulted in imbalance of Thl/Th2and Th17/Treg, promoting Thl-type immune responses in A A, and the immune system was overactive, all of which confirmed the fact that T-cell’s abnormal activation and proliferation played the crial role in the Immunological pathogenesis of the hematopoietic failure in patients with AA.Compare the changes of transcription factors of CD4+T cell subsets in MDS-RA and AA patients, there was no significant statistical difference, which indicate that there is a sthenic immune response of Thl in some patients with low-risk MDS groups like AA, which may be related to T cell stimulation from the clones of malignant hematopoietic cells. Immunosuppressive therapy can improve BM function and the quality of their lives.The immune stataus is different in MDS-RA and MDS-RAEB.With the progression of the disease, malignant clone in vivo increases, the low immunity can not eliminate tumor cells effectively, which can cause the disease to progress rapidly and even to turn into acute myeloid leukemia.The results of AML group is similar with MDS-RAEB group, the body’s celluar immune function continue to decline and the number cells which have the function of anti-tumor decrease,all of these make the body’s immune function of this stage present further suppress.