Changes of Intracellular Signal Pathway of mTOR/S6 in T Cells of Low-Risk Myelodysplastic Syndromes

Objects: To explore the state of of intracellular signal pathway of mTOR/S6 in FAB low-risk myelodysplastic syndrome-refractory anemia (RA)/RA with ringed sideroblasts (RAS).

Methods: Samples were collected from 18 MDS-RA/RAS patients. The intracellular percentages of p-mTOR, p-S6 and IFN-γ of CD3⁺, CD3⁺CD8⁺ and CD3⁺CD8⁻ T cells in bone marrow were detected by flow cytometry (FCM). 10 iron deficiency anemia (IDA) patients [male: 3, female: 7, media age: 44 years (from 31 to 72 years)] were determined as case controls and normal controls respectively.

Results

1. In normal controls, measurement of p-mTOR, p-S6 and IFN-γ in CD3⁺, CD3⁺CD8⁻ and CD3⁺CD8⁺ T cells were (1.54±1.51)%, (1.94±1.08)%, (2.04±2.03)%; (0.83±0.82)%, (0.91±0.88)%, (0.95±0.93)%; (4.42±3.55)%, (2.35±1.69)%, (4.73±4.43)%, respectively.

2. By 2.62%) of normal controls, MDS group could be divided into two subgroups: MDS-1 with a higher CD3⁺p-mTOR⁺ expression, and MDS-2 with a lower expression. In MDS-1, percentages of p-mTOR, p-S6 and IFN-γ in CD3⁺, CD3⁺CD8⁻ and CD3⁺CD8⁺ T cells were (20.70±18.02)%, (22.94±19.70)%, (26.03±22.91)%; (2.85±2.36)%, (3.36±2.84)%, (4.91±3.88)%; (13.92±12.87)%, (10.05±9.77)%, (16.38±15.49)%; which were higher than normal controls (P<0.05). In MDS-2, the percentages of CD3⁺p-mTOR⁺ [ (0.28±0.28)% ], CD3⁺CD8⁻p-mTOR⁺ [ ( 0.46±0.41 )% ], CD3⁺CD8⁺p-mTOR⁺ [ ( 0.47±0.44 )%], CD3⁺p-S6⁺[(0.21±0.21)%] and CD3⁺CD8⁻p-S6^+[(0.17±0.14)%] were lower than those of normal controls (P<0.05) respectively, whlie there were no significant differences in expression of IFN-γ in T cells [ (12.85±12.47)%, (7.11±7.02)%, (20.29±19.84)%] and p-S6 in CD3⁺CD8⁺ cells [0.65±0.64)% ] (P>0.05).

3. Upon RAPA treatment, in CD3⁺, CD3⁺CD8⁻ and CD3⁺CD8⁺ T cells of MDS-1 group, p-mTOR was inhibited more than 50% in 5of 10 cases; p-S6 was inhibited in 2, 4, and 6 cases, respectively, and IFN-γ was inhibited in 4, 4, 3 cases respectively.

Conclusions

1. In FAB low-risk MDS, the signal pathway of mTOR/S6 was activated, and it was quiescent in normal controls,.

2. The expression of p-mTOR, p-S6 and IFN-γ of this signal pathway in FAB low-risk MDS was heterogeneous.

3. RAPA could suppress mTOR/S6/IFN-γ in partial patients with low-risk MDS.