Lation between levels of miR-125b and Bak1 and obtained strongLation between levels of miR-125b and

Lation between levels of miR-125b and Bak1 and obtained strong
Lation between levels of miR-125b and Bak1 and obtained strong evidence that miR-125b could directly inhibit Bak1 expression in pediatric APL. Taken together, these Pamapimod molecular weight findings suggest that up-regulated miR-125b may be part of a common regulatory pathway in different cancers. Furthermore, exogenous miR-125b is capable of promoting proliferation of malignant cells. This finding indicates that miR125b may function as an oncogene by inhibiting APL cell apoptosis and promoting APL cell proliferation. Although conventional therapy, such as the modified PETHEMALPA99 protocol, succeeded in obtaining long term CR in more than 70 of APL patients, early death and relapse in some patients are still a major concern in therapeutics, especially for pediatric APL. However, the mechanism of the patients’ resistance to chemotherapeutic treatment is not entirely clear. Therefore, distinguishing the reason behind drug resistance and developing biomarkers are critical. We have shown that miR-125b differentially expressed between pediatric APL primary, CR and relapse patients, suggesting a potential that high miR-125b expression might be used as a biomarker to indicate the treatment response of pediatric APL patients, although the detailed mechanism is still unknown. More importantly, transfection of NB4 and HL60 cells with miR-125b effectively inhibited apoptosis of these leukemic cells. Previously, M. Bousquet et al. reported that miR-125b was able to block the differentiation of NB4 cells induced by ATRA [39]. Recently, miR-125b was also found associated with drug resistance in breast cancer and pediatric acute lymphoblastic leukemia [42,43]. In this study, we also demonstrated that up-regulation of miR-125b in pediatric APL cells can increase their resistance to therapeutic drugs. We speculated that increased miR-125b expression might block the differentiation of hematopoietic precursors and respond to induction by ATRA or other chemotherapeutic drugs. The expression of miR-125b both in pediatric and adult leukemia is currently not well understood. In adult APL,M. Bousquet et al. showed that myelodysplastic syndrome and AML patients carrying the t(2;11)(p21;q23) translocation were associated with miR-125b up-regulation [39]; however, they only studied 19 adult leukemia patients carrying the t(2;11)(p21;q23) translocation and did not determine whether the expression of miR-125b was up-regulated in adult APL patients. Another miRNA expression profiling assay suggested that miR-125b was up-regulated in seven adult APL patients, but this was not validated [44]. Thus, miR-125b expression should be further examined on a large scale with adult APL patients. Remarkably, in our large-scale qRT-PCR assay using 131 pediatric primary AML samples (M1 to M6), we found that miR-125b was exceptionally highly expressed in the pediatric APL subtype compared with other AML subtypes. Because pediatric AML is a heterogeneous disease made up of various leukemia subtypes that differ markedly in their cytogenetics, the identification of these specific cytogenetic characteristics within each subtype will be helpful for elucidating the mechanism of oncogenesis in particular AML subtypes. Furthermore, this information may benefit the design of chemotherapeutic strategies for patients. In conclusion, this is the first study of miR-125b expression in pediatric APL patients. Our results suggest that miR-125b might be used as a biomarker of malignancy and as a biomarker to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28300835 evaluate the.