Bone marrow overexpression of SNAI1 is an early indicator of intrinsic drug resistance in patients with de novo acute myeloid leukemia.

BACKGROUND: The lack of effectiveness of acute myeloid leukemia (AML) treatment remains a major challenge and resembles a principal cause of AML-related mortality owing to chemotherapy resistance. SNAI1 has been proved to be a leading factor in drug resistance in many cancer types. However, its relation to chemoresistance in AML is not well understood. METHODS: In addition to standard lab work, the expression level of SNAI1 was determined in bone marrow samples of 109 adult and pediatric patients with de novo acute myeloid leukemia using RT-qPCR. The relation between SNAI1 and AML drug resistance and immunomodulatory genes was investigated using the STRING tool. RESULTS: The SNAI1 expression level was upregulated in AML patients in particular samples with promyelocytic leukemia subtype against control cases. In the treatment response, SNAI1 was significantly higher in resistant patients in comparison with the complete remission group. SNAI1 overexpression was associated with high initial blasts and total leukocyte counts, but with HLA class II histocompatibility antigen DR downregulation. STRING analysis showed that multiple drug resistance and immunomodulatory genes of AML induce SNAI upregulation and activation. Kaplan-Meier analysis indicated that there was no relation between SNAI1 expression level and patient survival status. CONCLUSION: We conclude that the SNAI1 expression level may be a predictor of intrinsic drug resistance incidence in AML patients.

Inhibitory effect of N-acetyl-seryl-aspartyl-lysyl-proline on epithelial-mes-enchymal transition by heat-shock protein 27/zinc finger proteins / 中国病理生理杂志

AIM: To detect whether N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits epithelial-mes-enchymal transition in A549 cells induced by TGF-β1 through suppressing the expression of heat shock protein 27 (HSP27) and zinc finger proteins Snail (including SNAI1and SNAI2) which ultimately inhibited the deposition of type I and type III collagens.METHODS:The colocalizations of HSP27 and SNAI1/SNAI2 respectively on A549 alveolar epi-thelial cells induced by TGF-β1 were measured by confocal microscopy .The expression of HSP27, SNAI1 and SNAI2 at mRNA level was detected by real-time PCR.Western blotting analysis was used to detect the expression of HSP 27, SNAI1 and SNAI2 on epithelial-mesenchymal transition in A549 cells induced by TGF-β1 and also the deposition of type I and type III collagens in A549 cells transfected with HSP27shRNA prior to TGF-β1 stimulation.RESULTS: Compared with control group, TGF-β1 increased the expression of HSP27, SNAI1, SNAI2, type I and type III collagen, which decreased significantly followed by Ac-SDKP intervention.The expression of SNAI1, type I and type III collagen decreased signifi-cantly after transfected with HSP27shRNA in A549 cells, which had the similar effect on Ac-SDKP intervention.CON-CLUSION:Ac-SDKP inhibits the transition of cultured A 549 cells to myofibroblasts and attenuates collagen synthesis by suppressing the expression of HSP 27 and zinc finger proteins SNAI 1 and SNAI2.