Impact of FLT-3 mutations on clinical features and response to the therapy in acute promyelocytic leukemia patients

FLT3 mutations are associated with poor outcome in acute myeloblastic leukemia [AML] patients. Only limited information is available about effects of FLT3 mutation on Acute Promyelocytic Leukemia [APL]. We investigated the prevalence and impact of FLT3 mutations on the clinical characteristics and the response to treatment in APL patients treated with arsenic trioxide [As[2]O[3]]. Blood samples were collected from 115 untreated APL patients and genomic DNA was extracted by the salting-out method. FLT3-ITD and FLT3-D835 mutations were investigated by PCR-RFLP. Mann-Whitney U test and Chi-square were used for data analysis. FLT3-ITD and FLT3-D835 mutations were detected in 16 [14%] and 13 [11%] of the patients, respectively. Both mutations were identified in two patients, so overall frequency of FLT3 mutations was estimated to be 23.5%. Patients positive for FLT3-ITD mutation had a higher rate of white cell counts [p= 0.005] and more frequent bcr3 type of PML/RARA fusion [p=0.04]. We have not found any significant association between FLT3-D835 mutation and the clinical characteristics of patients. Between the group with FLT3 Mutations and the group without, there was no significant difference in response to therapy. Complete remission induction with As[2]O[3] may be independent of FLT3 mutation status, so As[2]O[3] may be the first choice of APL especially in patients with FLT3 mutations. However, further studies on a large group of patients are necessary to confirm our findings

[Effect on alpha hemoglobin chain expression in K562 cell line]

MicroRNAs [miRNA] are small noncoding RNA molecules that transcribed by RNA polymerase II. After biogenesis, these molecules act by incorporation into the RNA-induced silencing complex [RISC]. MiRNAs are involved in multiple physiological and pathological processes such as proliferation, differentiation, apoptosis and cancer. Recently several studies reported down regulation of mir-150 during erythropoesis. Since hemoglobin expression is valuable indicator of erythroid differentiation we evaluated the mir-150 downregulation effect on alpha chain expression by Quantitative RT-PCR. K562cells were grown in RPMI1640 in standard condition. K562 cells were transfected by microRNA 150 Inhibitor using transfection kit .Mir-150 downregulation was confirmed by miRNA Real time PCR, followed by Q-RT-PCR to investigate the alpha chain expression changes. By relative QRT-PCR the alpha chain expression was increased 10 folds in comparison to untransfected and scramble cells. Furthermore, the differences were statistically significant [P<0.05] Elevation of alpha chain expression in our study showed that mir-150 downregulation has a crucial role in erythroid differentiation and can introduce as a novel marker in alpha thalassemia. Further researches to find out the detail mechanism and miRNAs genes target could improve our knowledge about miRNAs potential in management of diseases and their applications in gene therapy and regenerative medicine

[Evaluation of the association of NOD2 gene polymorphisms with the occurrence of GVHD in acute myelogenous leukemia patients]

Graft-versus-host disease [GVHD] is one of life-threatening post-transplantation complications. Several recent studies have described a significant correlation between transplantation outcome and three single nucleotide polymorphisms [SNPs] in the NOD2 gene. This study was conducted to evaluate the association of NOD2 gene polymorphisms with the occurrence of GVHD in acute myelogenous leukemia patients who underwent HSCT from their HLA-matched sibling donors. We examined retrospectively NOD2 genotypes by PCR-SSP both in 124 patients who underwent HSCT and in their donors; then, the association of the genetic polymorphisms on acute and chronic GVHD was evaluated. Median follow up of patients was 40 months [range of 28-77 months]. Statistical analyses were performed using Chi-square test and SPSS software. Mutation incidence were the same between donors and recipients as 12.1%. In three of the patient-donor pairs [2.4%] SNPs occurred in both resulting in an overall frequency of 21.8% in patient-donor pairs. There weren't any significant differences between aGVHD and cGVHD incidence rates when donor/recipient pairs with SNPs were compared with the pairs without SNPs. aGVHD and cGVHD incidence rates in the former pairs were 52% and 56% and in the latter pairs 50.5% and 55%, respectively. No impact of NOD2 SNPs on incidence of acute and chronic GVHD was observed. Further studies are required to ascertain whether the findings of this study can be extended to other disease groups. In addition, further studies are required to identify the relevance of other SNPs