Background: acute lymphoblastic leukemia (ALL) is the most worldwide common type of childhood cancer. Methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) participate in folate pathways and are known as critical factors for DNA integrity as well as DNA hypomethylation. The aim of this work is to investigate frequency of MTHFR (677C -> T and 1298A -> C) and MTR (2756A -> G) polymorphisms and their interaction with respect to possible effect on risk of childhood ALL among North Indian population. Procedure: A case control study from has been conducted on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls using PCR-RFLP method. No statistically significant differences were observed for different genotypes between patients and controls (p >> 0,05). Significant difference for the risk of ALL in individuals having genotype of MTHFR 677TT (OR = 0,61, 95 % CI = 0,21 - 1,77) and MTHFR 1298CC (OR = 0,56, 95 % CI = 0,18 - 1,68) was not observed. The correlation of SNP of MTR gene and risk of ALL was not observed, too. Conclusions: the differences in distribution of possible combined genotypes of MTHFR (677C -> T, 1298A -> C) and MTR (2756A -> G) between ALL patients and controls were statistically insignificant.

In acute myeloid leukemia (AML)the functional abnormalities of osteopontin (OPN), NF-kB, PI3K/AKT/mTOR/PTEN pathway or beta-catenin have been considered. Aim - to analyze the response of U937 cells to parthenolide (PTL) through the involvement of expression of OPN protein, Relit. AKT1, mTOR, PTEN and beta-catenin genes. The U937 cells were treated with PTL at concentrations of 4 mu M (IC25) or 6 mu M (IC50) and with OPN siRNA for MTT assay and colony forming assay. Western blot analysis using antibodies against OPN was performed with lysates of PTL-treated cells. Quantitative real-time polymerase chain reaction was performed using primers for OPN siRNA, RelB, AKT1, mTOR, PTEN and beta-catenin. PTL reduces OPN protein level and down-regulates RelB mRNA in U937 cell line. Suppression of OPN with siRNA increases the cytotoxic effects of PTL. Also, mRNA expression of AKT1, mTOR, PTEN, and beta-catenin decreases with PTL or OiW siRNA. Conclusion: sensitivity of U937 cells to PTL can be associated with the reduction in expression of prosurvival mediators.

Індекс рубрикатора НБУВ: Р733.569.411 + Р733.411.022

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Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ