Evaluation of microRNA-146a expression in acute lymphoblastic leukemia

MicroRNAs （miRNAs） play an essential role in the development and progression of acute lymphoblastic leukemia （ALL）, and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high （18.75%）, low （27.08~o） and not different （54.17%） in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes （P190 and some translocations） with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients. We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.

Incidence of T3151 mutation in BCR/ABL-positive CML and ALL patients

OBJECTIVES： Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib （IM） has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients. METHODS： To conduct this study, 60 BCR-ABL-positive patients （including 50 CML and 10 ALL patients） who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS- PCR on cDNA and its polymorphism was evaluated by sequencing. RESULTS： The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation. CONCLUSIONS： The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T3151 patients, it can be concluded that ARMS- PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.

Factor XIII VaU34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population： a case control study

BACKGROUND： Recurrent pregnancy loss （RPL） is a heterogeneous condition and thrombophilias have been considered as a probable cause. OBJECTIVE： The aim of this study was to investigate the prevalence of the coagulation factor XIII Va134Leu polymorphism among women with unexplained RPL. METHODS： A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Va134Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. RESULTS： Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls （P〈 0.05）： 33.5% vs. 15%, and 9.2% vs. 2%, respectively. CONCLUSION： These results indicate a significant association between FXIII Va134Leu polymorphism and unexplained RPL in the Iranian patient.

MicroRNAs in erythropoiesis and red blood cell disorders

MicroRNAs （miRNAs） are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiation process of erythroid progenitors to nucleate red blood cells. Maturation, proliferation and differentiation of red blood cells is affected by erythroid factors, signaling pathways in niche of hematopoietic cells, transcription factors as well as miRNAs. Expression of different types of miRNAs during erythroid development provides a background for the study of these molecules to control erythroid differentiation and maturation as well as their use as diagnostic and prognostic markers to treat erythroid disorders like thalassemia, sickle cell disease and erythrocyte enzyme deficiencies. In this paper, with reference to biosynthesis of miRNAs, their function in normal and anemic erythropoiesis has been investigated. The target molecule of each of these miRNAs has been cited in an attempt to elucidate their role in erythropoiesis.