Part I: CD4~+CD25~+Foxp3~+ Regulatory T Cell-mediated Immune Escape Mechanism Of Acute Myeloid Leukemia Part II: Analysis Of The Efficacy Of Imatinib In Ph-positive Acute Lymphoblastic Leukemia

Objective:To detect the frequencies of Tregs,the migratory ability and the inhibitory effects on effector T cells of Tregs in patients with acute myeloid leukemia(AML),and to explore the possible upstream factors of Tregs' abnormalities in patients with AML.Our study would clarify the role of Tregs in immune escape of AML and find a novel target of immunotherapy for improving clinical efficacy of AML.Methods:?The frequencies of Tregs and the expressions of PD1,CTLA4 and GITR on the surface of Tregs were detected by flow cytometry(FACS).?The migratory ability was detected by chemotaxis assays.?The expressions of CXCR4 and CXCR7 on the surface of Tregs were detected by FACS and the concentrations of SDF-la were measured by ELISA.?Tregs were co-cultured with CD4 + T cells or CD8+T cells,and criss-cross co-culture experiments were carried to evaluate the inhibitory effects of AML and normal Tregs to immune cells.?Bregs were co-cultured with CD4+CD25-T cells,and criss-cross co-culture experiments were carried to address the efficiency of Bregs-mediatd conversion for Tregs.Results:?The frequencies of Tregs in peripheral blood and bone marrow in patients with AML were increased compared with healthy controls.?The migratory capacity of PB Tregs toward bone marrow in patients with AML was increased compared with healthy controls.?The enhancement of migratory capacity in patients with AML increased was due to higher expressions of CXCR4 on PB Tregs.?AML Tregs were more capable in inhibiting the proliferation and promoting the apoptosis of CD4+T cells compared with healthy controls.What's more,AML Tregs could more suppress the production of INF-?.?AML Bregs could induce the conversion of CD4+CD25'T cells to CD4+CD25+Foxp3+ Tregs.Conclusions:Our study revealed that Tregs in patients with AML had higher frequencies,increased migratory capacity toward bone marrow and more capable in inhibiting the proliferation,promoting the apoptosis and suppressing the cytokine secretion of CD4+T cells.Bregs in AML patients could induce the conversion of CD4+CD25'T cells to CD4+CD25+Foxp3+ Tregs and amplify the immunosuppressive effects of Tregs,thereby providing a theoretical basis of immunotherapy for AML.Objective:To explore the efficacy and prognostic factors of imatinib(IM)combined with chemotherapy for BCR/ABL1 gene positive acute lymphoblastic leukemia(ALL).Methods:A total of 209 BCR/ABL+ ALL patients treated with imatinib plus chemotherapy from April 2003 to August 2015 were enrolled in the study,and 106 patients underwent hematopoietic stem cell transplantation(HSCT).Results:The complete remission(CR)rate was 97.9%in newly diagnosed patients.WBC?100×109/L on diagnosis was a poor factor for overall survival(OS)(P = 0.043).Without HSCT,no CR within 4 weeks in the first cycle induction chemotherapy and never achieving complete molecular remission(CMR)during the treatment were adverse factors for OS(P =<0.001,0.009 and<0.001,respectively),as well as for relapse free survival(RFS)(P =<0.001,<0.001 and<0.001,respectively).Of the 106 patients who underwent allo-HSCT or auto-HSCT,there was no statistically significant difference of the OS and RFS.There was no significant difference of OS in patients combined imatinib or not in the induction chemotherapy,but the former showed higher 5-year RFS rate(37.0%vs 24.0%,P = 0.005).The survival of the patients who took tyrosine kinase inhibitors(TKIs)regularly and continuously was the best,followed by those who interrupted TKIs during the bone marrow suppression,with patients taking TKIs irregularly the worst.The 5-year OS rates among three groups were 46.0%,28.0%and 17.0%,respectively(P ? 0.004).The 5-year EFS rates among three groups were 38.0%,28.0%and 17.0%,respectively(P<0.001).Conclusions:TKIs plus chemotherapy followed by HSCT improved the prognosis of the patients with BCR-ABL+ ALL patients.It is important to administer TKIs regularly and continuously to improve the outcome of BCR-ABL+ ALL patients.