The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.

No abstract

These results could facilitate the prediction and development of more effective drugs for Top2-α variants, making the cancer chemotherapy more effectiv.

DFG, αC-helix orientation regarding the active site position and distance between K54 and Glu71 in the active and inactive states of ERK2.

Objective: This study was aimed to investigate the association between polymorphisms in MTHFR gene and Vitamin B12-dependent homocysteine metabolism.Methods: Hyperhomocysteinemia has been implicated as a risk factor for complications in pregnancy including abortion, preeclampsia, and placental abruption. Several epidemiological studies have investigated the associations of MTHFR C677T polymorphism with hypertension or hypertension in pregnancy. However, the results were controversial. Numbers of 100 samples from healthy pregnant women as control criteria and 100 samples from fertile women have been collected. Due to research on MTHFR polymorphism, special primers have been designed. The research on MTHFR polymorphism has been done by restriction fragment length polymorphism assay.Results: The results demonstrated 9.26% have been registered for heterozygous individuals and the homocysteine level of homozygous individuals was 41.18% (higher than the normal level). The results showed a significant difference in the homocysteine levels of homozygous individuals and the homocysteine levels of healthy individuals (p=0.004). Furthermore, there was no significant difference in the homocysteine levels of heterozygous individuals and the homocysteine levels of healthy individuals (p=0.34). Similarly, a significant difference in the B12 levels in blood of homozygous individuals and the homocysteine levels of healthy individuals have been showed (p=0.00).Conclusion: The mutation of gene MTHFR C677T causes an increase of the homocysteine level, decrease of the level of folic acid and B12 vitamin in heterozygous individuals but a relationship among homocysteine level, the level of folic acid and B12 vitamin not found.