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Background & Objective: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by an aberrant BCR-ABL fusion protein. Imatinib mesylate (IM) is a tyrosine kinase inhibitor that induces clinical remissions in chronic-phase CML patients. The T315I mutation at the gatekeeper residues of BCR-ABL confers resistance to both IM and second-generation TKIs, including dasatinib and nilotinib. Our objective was to determine the prevalence of T315I mutation between two groups of CML patients before and during Imatinib treatment in North-East of Iran. Materials & Methods: This study was conducted on 100 newly diagnosed cases of CML (before commencing IM treatment) and 25 IM-resistant CML patients. PCRRFLP, ASO-PCR, and direct sequencing were performed to detect T315I mutations. Results: The median age of newly-diagnosed and IM-resistant patients was 48±14 and 50±12.3 years, respectively. Males/Females ratio was 1 and 1.08 for newly diagnosed and IM-resistant patients, respectively. There was no significant difference regarding the age and sex between the two groups. During the study, T315I mutational analysis was performed for all 125 patients. The prevalence of T315I mutation was 0% and 4% for newly-diagnosed and IM-resistant patients, respectively. T315I mutation was not detected before IM administration, although it was detected in 1(4%) among resistant patients who were at least 6-months on IM treatment. Conclusion: These observations suggest that T315I mutation may be categorized as secondary resistance and induce clonal expansion due to BCR/ABL instability. Hence, BCR-ABL mutations [ABSTRACT FROM AUTHOR]

Genetic variations in the vitamin D-binding protein (VDBP) may be associated with the plasma level of serum 25-hydroxyvitamin D. Furthermore, vitamin D deficiency increases the risk of acute myeloid leukemia (AML). This study aimed to examine the potential association of VDBP genetic variants (rs7041 and rs4588) with AML susceptibility. The polymorphisms in the VDBP gene and serum 25-hydroxyvitamin D levels were analyzed in 227 AML patients and 240 healthy controls enrolled in this study. Our data revealed that rs4588 CA and AA genotypes were significantly associated with AML susceptibility (OR = 1.483, p = 0.046; OR = 2.154, p = 0.013, respectively) and also with 61.59% vitamin D deficiency in the total group of AML patients. Under the TG co-dominant and dominant models, however, the rs7041 genotypes were significantly associated with AML protection (OR < 0.6; p < 0.05). In addition, vitamin D deficiency was prevalent in vitamin-D-deficient vs. sufficient AML patients who carried rs7041 and rs4588 mutant alleles (OR ≥ 2.2). Indeed, vitamin D deficiency and its interaction with the genetic variants of VDBP could change the risk of AML. Thus, vitamin D deficiency could be considered an important molecular factor in AML risk assessment. [ABSTRACT FROM AUTHOR]

Background: Bone marrow transplantation (BMT) is considered as a curative therapy for a broad range of diseases. However, complications such as relapse and graft versus host disease (GVHD) may be observed following BMT. Chimerism analysis serves as a reliable indicator of transplant outcome. Complete chimerism refers to the complete replacement of hematopoietic system by donor cells, while mixed chimerism is the coexistence of both donor and recipient cells. The current study aimed to assess the relationship between molecular chimerism and GVHD as well as relapse and survival after allogenic hematopoietic stem cell transplantation (allo-HSCT) using Short Tandem Repeat-Polymerase Chain Reaction (STR-PCR). Material and Methods: This retrospective survival study was performed on 30 patients (Median age: 11.57±6.83 years) including 12 (40%) children with acute leukemia (6 patients (50%) acute myeloid leukemia and 6 patients (50%) with acute lymphoblastic leukemia patients). All patients received allo-HSCT during 2012-2016 at Montaserie Hospital, Mashhad, Iran. Chimerism analysis by STR-PCR method was carried out at cancer molecular pathology research center of Qaem hospital, Mashhad, Iran. Chimerism was assessed using 7-STR markers on recipients' bone marrow aspiration samples on day 14 or 15 after BMT. Results: The findings indicated that the mean chimerism level in patients with skin GVHD was significantly different compared to cases without skin GVHD (P=0.02). It was also found that patients' survival was significantly longer in cases with complete chimerism (P=0.04). Conclusion: Chimerism analysis may permit early prediction and monitoring of post-transplant complications such as GVHD, transplant rejection, and relapse and assist clinicians to proceed with suitable treatment plans. [ABSTRACT FROM AUTHOR]

Introduction: Hearing impairment is a complex medical disorder which has genetic and non-genetic causes. Gap Junction Protein Beta 2 (GJB2) gene variant is a well-known disease-causing gene among patients with hearing impairment. The frequencies of genetic variants in the GJB2 gene are different in each population. This study aimed to discuss the GJB2 gene status in an Iranian population with hearing impairment who referred for prenatal testing. Materials and Methods: This cross-sectional study was conducted in a genetic laboratory affiliated with Mashhad Jahad Daneshgahi, Mashhad, Iran. A total number of 21 bilateral hearing impaired patients were enrolled in this study. The exons for target GJB2 gene were amplified by polymerase chain reaction after the confirmation of the hearing impairment and the exclusion of the acquired causes of hearing loss. Results: The c.35delG and c.79G>A variants were the first and second most common variants in the study population, respectively. The mean age of the patients was 27.5 (8.7) years and 12 cases were male. There was no significant association between hearing impairment degree and age and heterozygosity status (P=0.376 and P=.074 respectively). Conclusion: The c.35delG and c.79G>A variants were determined as the first and second most common variants in the GJB2 gene, respectively. The mean age of 26 years in this study population indicates the late referral for the evaluation of the hearing difficulty. Furthermore, it highlights the further need to encourage families with a history of hearing impairment to engage in genetic counseling. [ABSTRACT FROM AUTHOR]

Background and Objective: Janus kinase 2 (JAK2) and Myeloproliferative Leukemia (MPL) mutations are confirmatory indicators for Myeloproliferative Neoplasm (MPN). The current study was performed to determine the frequency of MPL mutation in MPN patients without JAK2 mutation, in order to assign MPL mutation frequency in North-East of Iran. Methods: Total of 105 negative JAK2 cases including 5 Myeloproliferative Disorders (MPD), 15 Polycytemia Vera (PV) and 15 Essential Thrombocytosis (ET) who referred to Qaem Medical Center were assigned to this study. ARMS-PCR was carried out for measuring MPL mutations. Results: A significant difference was observed between MPL mutant and non-mutant groups from overview of MPL mutation (P=0.00001). From the total studied population, 14.28% were ET cases and 4.71% of them had splenomegaly. About 66.66% had thrombocytosis and 33.33% of all the individuals had leukocytosis according to WHO criteria, and 4.76% of non-MPL mutant individuals had splenomegaly (P=1). This mutation was reported in 4-6% of ET and PMF individuals. In this research, 4.76% of studied individuals had MPL (W515L/K) mutation, which were diagnosed with ET. Conclusion: Generally, the presence of JAK2 and MPL mutations are the most important criteria for MPN diagnosis. The obtained frequency of MPL mutation was similar to previous studies. Despite the high frequency of JAK2 and Philadelphia abnormality, MPL mutation was rare in myeloprolifrative disorders. Further studies are suggested to investigate its prognostic effects for these diseases. [ABSTRACT FROM AUTHOR]

Objective(s): Sulfur mustard (SM) was used by the Iraqi army against the Iranian troops in the Iran-Iraq war from 1983-1988. This chemical gas affects different organs including the skin, lungs and the hematopoietic system. Any exposure to SM increases the risk of chromosomal breaking, hyperdiploidy and hypodiploidy. Studies have shown that the risk for acute myeloblastic and lymphoblastic leukemia increases in veterans exposed to SM. FLT3 mutations including ITD and TKD mutations had been observed in some cases of leukemia. Therefore, we aimed to investigate the frequency of FLT3- TKD835 mutations in the veterans exposed to SM agent. Materials and Methods: We studied 42 patients who were exposed to SM during the war in Khorasan Razavi province, Mashhad, Iran in 2012. As control group, 30 healthy males were selected from firstdegree relatives of the patients. For assessment of TKD835 mutation, DNA was extracted and RFLPPCR was performed. Results: Analysis of RFLP-PCR data showed no FLT-3 TKD mutation in any of the patients. Conclusion: Although contact with SM can increase the risk of malignancy especially hematologic neoplasms, results of the study show that another mechanism of leukemogenesis, other than FLT3- TKD mutation, may be the reason for increased risk of leukemia in SM toxicity. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is recognized as one of the most common types of leukemia among adults. This condition is characterized by the uncontrolled proliferation of myeloid progenitors, affecting the normal function of different systems in the human body. Various factors such as genetic abnormalities, exposure to chemicals, and viruses can induce AML. Expression of NPM1, CEBPA, MN1, and BAALC genes is among important genetic factors affecting AML prognosis and diagnosis. The aim of this study was to assess amount of BAALC gene expression in AML patients and its relation to survival rate. This case-control study was performed at Mashhad University of Medical Sciences, Mashhad, Iran. 56 AML patients and 56 healthy individuals were participated in this research. The level of BAALC gene expression was assessed by real-time polymerase chain reaction (RT-PCR) method; GPI gene was used as the control. For statistical analysis, SPSS version 21 was applied. P-value less than 0.05 was considered statistically significant. In total, 55.3% and 44.7% of the participants were male and female, respectively. BAALC gene up- and down-regulation was reported in 28.6% and 71.4% of AML cases, respectively. BAALC gene expression and hematological parameters were significantly different between the two groups (p< 0.05). Based on the findings, the survival rate was estimated at 31 and 39 months in patients with BAALC up- and down-regulation, respectively. BAALC gene over expression could be considered as a predictive factor for poor prognosis and reduced survival in AML patients. [ABSTRACT FROM AUTHOR]