hossein ayatollahi

Comprehensive molecular assessment of cancers could open up new horizons for novel therapies. Fibroblast growth factor receptor 1 (FGFR1) gene amplification has been previously demonstrated in non-small cell lung cancer (NSCLC) patients. The current study aimed to evaluate the prevalence of FGFR1 gene amplification and its association with clinical and demographic data in a group of NSCLC patients.

The present study was performed on eighty-eight NSCLC patients who underwent bronchoscopy or surgery in Qaem Hospital, Mashhad, between 2010 and 2016. FGFR1 gene amplification was detected using real-time PCR assay on DNA extracted from paraffin-embedded tissue blocks of patients. Also, patients' clinical and demographic data, such as their survival, were evaluated. Statistical analysis was carried out using SPSS software.

Seventeen (19.31%) out of eighty-eight patients with NSCLC presented FGFR1 gene amplification. Besides, we found a significant association between FGFR1 amplification and cigarette smoking (p-value= 0.01; OR: 4.08). Although cases with squamous cell carcinoma (SCC) showed a higher prevalence of FGFR1 amplification compared to adenocarcinoma patients, the difference was not statistically significant (p-value> 0.05). In addition, our findings showed no relationship between FGFR1 gene amplification and other clinical and demographic factors, including age, sex, grade, tumor operability, and survival.

The frequency of FGFR1 amplification is estimated at 20% in the current study (26% in SCC versus 11% in adenocarcinoma; p-value= 0.07). Moreover, we found a direct association between FGFR1 amplification and cigarette smoking. However, no significant relationship with survival or other factors was observed.

NUP98 gene fusions in acute myeloid leukemia (AML) have recently attracted much interest. Despite substantial research illuminating the roles of NUP98 fusions in the course of AML, their impacts on the outcome of patients with AML should be explored in more detail. As a result, this meta-analysis was designed to provide further light on the prognostic implications of NUP98 fusions in AML.

We completed an extensive search in PubMed, Scopus, and Web of Science to identify papers evaluating the prognostic effects of NUP98 rearrangements in patients with AML until August 22, 2022. In total, 15 publications with 6142 participants fulfilled the requirements for the current meta-analysis. All the qualified studies were examined for information regarding HRs and 95% confidence interval (95%CI) for overall survival (OS) and event-free survival (EFS). In addition, we utilized Comprehensive Meta-analysis software version 2 (CMA2) for calculating pooled HRs and 95% CI.

Our analyses for NUP98-NSD1 indicated that this fusion could significantly impact the outcome of patients with AML (pooled HR: 2.84; 95% CI: 2.49–3.24, P=0.000). Additionally, we observed a strong correlation between NUP98-KDM5A rearrangement and poor prognosis in AML (pooled HR: 2.65; 95% CI: 2.5-2.81; P=0.000). A subgroup analysis also showed that the NUP98-NSD1 and FLT3-ITD together confer a poor prognostic effect (pooled HR: 2.60, 95% CI: 1.61-4.18; P=0.000).

NUP98 fusions could significantly impact the outcome of patients with AML. The use of these fusions as prognostic indicators in AML seems rational.

Subclinical hypothyroidism (SCH), is defined as an asymptomatic state characterized by a normal serum concentration of free thyroxine and elevated serum concentration of TSH. This study aims to investigate the complex interplay between hyperinsulinism, insulin resistance, beta cell function, and low-grade chronic inflammation in Iranian women with SCH.

Eighty women with SCH and 80 healthy women as controls matched to the patient group for sex, age, and body mass index (BMI), were enrolled in this prospective cross-sectional study. TSH, free T3, free T4, highly sensitive C-reactive protein (hs-CRP), fasting insulin, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, HOMA-IR index, Beta cell function (HOMA-B index) and insulin sensitivity were determined.

Hs-CRP was not statistically different between the SCH patients and the control group (3.7±3.2 Vs 3.6±4.0, P>0.05). Total cholesterol and LDL-cholesterol were significantly higher; however, triglyceride and HDL-cholesterol were not statistically different in patients with SCH as compared with the control group. Fasting insulin levels and HOMA-IR and Beta cell function (HOMA-B) were significantly higher in SCH women compared to the control group. A positive correlation between HOMA-IR and HOMA-B with TSH levels was found (r=0.324, r=0.191, P<0.05 respectively). A positive correlation between insulin levels and hs-CRP (r=0.22, P<0.05), also between insulin levels and TSH (r=0.312, P<0.05) and LDL- LDL-cholesterol was obtained (r=0.27, P<0.05).

 Iranian women with SCH may exhibit elevated atherogenic parameters (hyperinsulinemia, LDL-cholesterol, and total cholesterol), HOMA-IR, and HOMA-B.

The current study intends to assess the impact of oral selenium intake on anti-Tg antibody in individuals with autoimmune hypothyroidism.

In this double-blinded randomized controlled trial, two groups of 72 autoimmune hypothyroid patients were randomly assigned; One group received levothyroxine (LT4) and oral selenium and the other group was given placebo with LT4. Anti-Tg antibody, free T4, anti-TPO antibody, and TSH were identified in both groups before the treatment and also 3 months after treatment and analysis of data was done by SPSS software.

After the intervention, the average amount of anti-Tg antibody decreased in both of the groups, and this decrease was noticeably greater in the intervention group (P = 0.03). In the intervention group, the TSH level decreased after the intervention (p < 0.05), and the free T4 level increased after the intervention (p < 0.05); the changes in these two variables were statistically significant.

Consumption of selenium, compared to placebo, in patients with autoimmune hypothyroidism drastically reduces the level of anti-Tg antibody, and it significantly increases the free T4 level. Also, there is a greater decrease in the level of TSH compared to the control group.

Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML.

We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and p-values were also calculated as a part of our work.

The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091).

ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue.

Autophagy is a pathway for the degradation of cytoplasmic components, which plays an essential role in various cellular and physiological processes, including cell renewal and survival, and immune responses. While recent studies have shown that they can play a role in cancer treatment, the precise mechanisms of autophagy in leukemogenesis are not fully understood. We have assessed the expression levels of LC3 and BECLIN1 as two crucial autophagy mediators in patients with leukemia.

This cross-sectional study was performed on bone marrow or peripheral blood samples of 61 leukemia patients (24 AML, 20 ALL, and 17 CML) and compared to 18 healthy controls. Real-time PCR was used to quantitate gene expression. SPSS statistics 16.0 and Graph Pad Prism 8.4.2 software were applied for statistical analysis.

While BECLIN1 expression was significantly lower in AML, ALL, and CML patients as compared to the control group (p < 0.05), LC3 showed significantly different expression only in the AML patients (P= 0.03). There was no significant correlation between the expression levels of BECLIN1 with LC3 (p> 0.05). Whilst the AML LC3high group had a significantly lower lymphocyte count (P= 0.023), the AML BECLIN1low group had a significantly higher MPV levels (P= 0.044). Furthermore, ALL LC3high group indicated a significantly lower HCT count (P= 0.017).

Significant changes in the expression levels of BECLINI and LC3 in hematologic malignancies may indicate a possible role for autophagy in their pathogenesis. However, further studies are warranted to confirm these findings.

Acute lymphoblastic leukemia (ALL) causes uncontrolled cell proliferation and prevents normal cell differentiation at any stage of hematopoiesis. Therefore, timely diagnosis and treatment are very important. Complete blood count (CBC) can be a simple, but valuable initial test to diagnose ALL. In this study, we investigated the diagnostic value of hematological parameters, including Platelet to lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin to Platelet ratio (HPR) indices in ALL.

In this study, 54 ALL patients (Mean ages: 5.29) and 58 healthy controls (Mean ages: 5.53) were evaluated. They were compared in terms of hematological parameters, including PLR, NLR, and HPR; cytogenetic and immunophenotypes were also analyzed.

In the analysis of hematological factors between the studied groups, all indices except lymphocytes showed a statistically significant relationship (P-Value ˂0.05). In terms of hematological factors, only WBC and ESR were statistically significant between the B-ALL and T-ALL groups (P-Value ˂0.05). The ROC curve was generated to select the appropriate cut-off values for NLR, PLR, and HPR based on analysis. NLR and PLR have cut-off values of 0.50 and 62.24, respectively; they are good biomarkers to distinguish ALL individuals from normal people. HPR value was significant between case and control groups, but it was not a suitable indicator for distinguishing patients from the control group.

CBC is a simple and valuable test for early detection of ALL, and the new PLR and NLR markers are good hematologic markers for ALL diagnoses.

Background &  Recurrent pregnancy loss (RPL) is the occurrence of three or more miscarriages before the 20th week of pregnancy. Thrombophilia factors are one of the common causes of RPL.Materials &  This retrospective study was performed on women with miscarriages. 620 patients’ documents with pregnancy loss were investigated. Based on the number of pregnancy loss, the women were divided into a control group with less than three miscarriages (212) and RPL group (180). Cytogenetics analysis and thrombophilia factors polymorphism tests were performed for all patients. In the analysis, none of the studied polymorphisms (MTHFR 677 C⁄T /Factor V Leiden /Prothrombin G20210A/ ACE I/D/ PAI-1) showed a significant relationship between Control and RPL groups (P-value ˃ 0.05). Cytogenetic analysis showed 2 numerical and 9 structural abnormalities among both groups. Statistical analysis indicated a significant association between the number of abortions and age (P value= 0.005, r= 0.139). We even realized that there was a significant relationship between polymorphism number and recurrent number of miscarriages (P value= 0.018, r= 0.6). We showed that polymorphisms analysis for thrombophilia factors is a more precious test than cytogenetics analysis (study of the banded pattern of chromosomes during metaphase of the cell cycle). We even indicated that no association was found between thrombophilia polymorphisms in the control and RPL groups. This means that screening for Factor V Leiden, prothrombin G20210A, MTHFR C677T, ACE I/D, and PAI-1 and cytogenetic analysis in patients with a history of RPL is not recommended.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accompanies a worse survival.  In this study, gene expression levels of 5 key players of apoptosis, including DR4, DR5, FAS, caspase 8, and DNA damage-induced apoptosis suppressor (DDIAS), have been evaluated in AML patients compared with controls, aiming to evaluate their possible role and prognostic impact.  

This cross-sectional study was performed in the Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. A total of 30 newly diagnosed AML cases as well as 30 healthy controls enrolled in the study. Real-time polymerase chain reaction was used to evaluate the expressions of DR4, DR5, FAS, DDIAS, and caspase 8 genes in cases and controls. Other necessary data, including cytogenetic findings, mutations, French-American-British (FAB) classification, and survival, were retrieved from hospital records and by direct contact with patients. Statistical analysis was done by SPSS software. When appropriate, the Mann-Whitney U, Pearson's correlation, and the t tests were utilized. Overall survival (OS) was estimated using the Kaplan-Meier method.  

The expression of all evaluated genes, including DDIAS (0.89 ± 0.20), DR4 (0.67 ± 0.24), DR5 (0.72 ± 0.24), FAS (0.70 ± 0.25), and Caspase 8 (0.77 ± 0.20) were significantly decreased in AML patients compared with the controls (P < 0.001). Patients with the t (16;16) or inv (16) expressed significantly higher amounts of the FAS gene and those with FLT3 mutation exhibited lower expression of caspase 8. Expression of the evaluated genes showed no significant effect on survival.  

The expression of DR4, DR5, FAS, and caspase 8 seems to be decreased in AML. Lower expression of these molecules may aid AML cells in avoiding apoptosis because they are involved in the initiation of apoptosis, making them potential targets for treatment.

 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.

 This study was conducted on 100 newly diagnosed cases of CML (before commencing IM treatment) and 25 IM-resistant CML patients. PCR-RFLP, ASO-PCR, and direct sequencing were performed to detect T315I mutations.

 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.

 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 are less likely to appear before the onset of treatment, as presented in our study.

Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progress of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes.

A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing.

While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group.

The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

The B-cell-specific Moloney murine leukemia virus integration site1 (BMI-1) is one of the famous members of the Polycomb ring finger group, which plays a crucial role in the gene transcription regulation through histone changes. Hence, it is believed to be necessary to further clarify the effects of the BMI-1 clinical.

This cross-sectional study was conducted on 70 acute myeloid leukemia (AML), 70 chronic myeloid leukemia (CML), and 20 healthy individuals, as the control group. We used real-time quantitative polymerase chain reaction in order to assess the BMI-1 level expression and its effect on prognosis in AML patients in the Molecular Pathology Research Center.

The results of the present work indicated that the BMI-1 overexpression was significantly higher in the AML and CML patients compared with that in the healthy controls (P < 0.001). Furthermore, a significant relationship was observed between the BMI-1 overexpression and poor prognosis in the AML patients (Hazard ratio=1.749, P < 0.001, 95% confidence interval = 1.31-2.32). Additionally, BMI- 1high was found in chronic and blastic phase in the CML patients (P < 0.001).

We concluded that investigation of BMI-1 gene expression pattern will be conducive to the prognosis and treatment of myeloid leukemia.

Fanconi anemia (FA) is an autosomal recessive disorder that usually manifest in forms of pancytopenia, hyperpigmentation, and skeletal complications. Mutation in the DNA repair regulatory genes is associated with the development of FA. Examination of chromosomal breakages when chromosomes are exposed to cross-linking agents is a common method of FA diagnosis. This study aimed to evaluate the prevalence and characteristics of patients with FA in Mashhad, northeast of Iran.

In this study, we evaluated 312 suspected FA patients who had been referred to the laboratory of Ghaem Hospital during 2014-2020. The mitomycin C method was used to identify FA-positive subjects.

After the examinations, 84 patients (26.9%) were cytogenetically positive for FA. Of 84 patients, 48 (57.1%) were male and 36 (42.9%) were female. Thumb abnormality was the most common congenital anomaly (43.2%).

Based on the findings, males are more susceptible to FA, and thumb abnormality is the most common congenital anomaly associated with FA. Combination of clinical manifestations and genetic susceptibility in patients may contribute to a more accurate diagnosis.

Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by genetic abnormalities. These days, molecular and genetic factors are usually used as diagnostic and prognostic markers. FLT-3 is one of the most known diagnostic factors in AML. MDR1 gene belongs to the ATP binding cassette family; it is known as one of the chemotherapy-resistant causes of AML. We aimed to study FLT-3ITD mutations and their association with MDR1 gene expression in AML individuals.

For investigation, 80 AML individuals and 20 healthy controls were selected. This study was done in the cancer molecular pathology research center of Mashhad University of Medical Sciences (MUMS), Iran during 2017-2019. FLT3-ITD mutation was assessed by polymerase chain reaction (PCR); Real-time quantitative PCR was performed to measure the amount of MDR1 gene expression. Bone marrow and blood smears of patients were evaluated in terms of morphology. SPSS 16.0 was used for data analysis.

FLT3-ITD mutation and MDR1 overexpression were found in 18.8% and 23.8% of AML patients, respectively. Statistical analysis did not show any relations or association between these two markers. Cuplike morphology was observed in blast cells in 21.25% of AML cases, which was associated with FLT3-ITD mutation presence.

FLT-3 and MDR1 do not affect each other. It is suggested to perform survival studies to determine the exact role of MDR1 overexpression in drug resistance issues.

Acute lymphoblastic leukemia (ALL) accounts for nearly 30% of pediatric cancers. The maintenance treatment for ALL comprises daily oral 6-mercaptopurine (6-MP) and weekly methotrexate (MTX). 6-MP is a purine analog that can significantly improve the long-term survival of ALL patients. Despite more than 90% of 5-year survival of childhood ALL in developed countries, treatment interruption due to drug toxicities continues to be a grave concern during therapy. Several studies have highlighted the association between some genetic variants and 6-MP toxicities in ALL patients. Some variants of 6-MP metabolizing enzymes received much attention as possible predictors of myelotoxicity following 6-MP therapy. Recently, two landmark genome-wide association studies have highlighted variants in nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) as promising indicators of 6-MP toxicities. It seems that NUDT15 genotyping can help determine the optimum dose of 6-MP and prevent toxicities, especially fatal myelotoxicity. No association was found between NUDT15 variants and hepatotoxicity or survival rates of ALL patients in previous studies. However, further studies are warranted to shed more light on these issues. The current review updates and evaluates the available scientific data regarding different genetic variants of NUDT15 and their possible roles in 6-MP intolerance in various ethnic groups.

The autophagy machinery is reported to be employed by Coronaviruses during their replication. Beclin-1 (BECN1) and protein 1 light chain 3 (LC3) are two key elements in the autophagy process, and their inhibition can prevent the replication of some coronaviruses in vitro. Here, we aimed to investigate the expression levels of Beclin-1 and LC3 in COVID-19 patients and healthy controls, hoping to find new therapeutic targets.  

This cross-sectional study was conducted in Imam Reza and Ghaem University Hospitals, Mashhad, Iran. Nasopharyngeal samples of 68 consecutive Covid-19 patients and 61 healthy controls, who have been referred to the laboratories for COVID-19 PCR testing between 21 March to 21 September 2021, were used in order to evaluate the expression of BECN1 and LC3 genes using the Real-time quantitative PCR method. Demographic and other laboratory findings of patients were extracted from the hospital electronic system. SPSS Statistics 16.0 and Graph Pad Prism 8.4.2 soft wares were used for statistical analysis. Non-parametric tests were used.  

BECN1 expression was significantly higher in COVID-19 patients compared to the controls (14.37±18.84 vs. 4.26±7.39, p=0.001).  The expression of LC3 gene was significantly lower in patients compared to the controls (1.01±1.06 vs. 1.49±1.12, p=0.007). There was no significant correlation between the expression levels of BECN1 and LC3. Patients with lower BECN1 expression showed significantly higher RBC counts, higher Urea and lower HCO3 levels. The patients in LC3Low group showed significantly lower MCH, MCHC and PH levels compared to the others.   

Regarding the significant difference in the expression of BECN1 and LC3 in COVID-19 patients compared to the controls, these molecules may have a role in the pathogenesis of this disease. In case of further confirmation of this role, these molecules may be used as possible therapeutic targets.

One of the major genetic causes of recurrent spontaneous abortions is parental chromosomal abnormalities. The objectives of the study were to determine, compare and analyze the incidence and distribution of chromosomal abnormalities in couples with recurrent miscarriages from Northeastern Iran.

This study was conducted at Ghaem Hospital, Mashhad, Iran. We evaluated karyotype results of 608 couples with history of recurrent spontaneous abortion. The standard method was used for culturing peripheral venous blood lymphocytes.

Chromosome aberrations were detected in 43 patients (3.54%), including 25 females and 18 males. Structural chromosomal abnormality was detected in 40 cases, including balanced translocations (25 cases), robertsonian translocations (4 cases), inversions (10 cases) and numerical chromosome aberrations (3 cases). Polymorphic variants were observed in 22 individuals.

The frequency of chromosomal abnormalities in couples with Recurrent Spontaneous Abortion (RSA) in our study is 3.54%. Reciprocal translocation, pericentric inversions, robertsonian translocations, and numerical abnormality observed among couples who had experienced recurrent spontaneous abortions and that these couples might benefit from cytogenetic analysis.

Chromosomal aberrations which occur in different hematologic malignancies are believed to be highly applicable for identifying the prognosis and treatment protocols. We conducted the present study to investigate the chromosomal and molecular abnormalities in bone marrow of acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and myelodysplastic syndrome patients.
We performed this cross-sectional study in molecular pathology and cancer research center of Mashhad University of Medical Sciences (MUMS), during 2017-2019; the total number of our cases was 252. We did all the molecular and cytogenetic tests on these patients. SPSS V.16 software was utilized for the analysis of our data.
In this research, the ALL patients were meaningfully younger than AML ones. There were significant associations between karyotype patterns and types of malignancy; normal diploid was more frequent in myelodysplastic syndrome (P<0.05). Among numerical abnormalities, trisomy 3 and monosomy 14 were the most prevalent ones.
The results of similar studies from different areas with different ethnics would help to identify new parameters for prognosis determination. Cytogenetic analysis is highly applicable for leukemia diagnosis and prognosis.

Acute lymphoblastic leukemia (ALL) is a highly heterogeneous malignancy that accounts for nearly 75% of leukemias in children. While the exact mechanism of ALL is not fully understood, some genetic variants have been implicated as associated with ALL susceptibility. The association between some genetic variants in miRNA genes and ALL risk has been described previously. A previous study suggested that mir-612 rs12803915 G> A may be associated with pediatric ALL risk. High-resolution melting (HRM) analysis is a reliable method that can be applied for polymorphism detection.

This retrospective study was performed on 100 B-ALL patients (52 males and 48 females; age 4.6 ± 3.2 years) and 105 age- and sex-matched healthy controls (48 males and 57 females; age 5.1 ± 3 years). We used HRM to identify mir-612 rs12803915 genotypes. Sanger sequencing was applied to validate the HRM results.

High resolution melting analysis was used to genotype the mir-612 rs12803915 polymorphism. We found no association between rs12803915 allele A and B-ALL risk in any inheritance models (p> 0.05).

HRM is a suitable method to detect SNP rs12803915 in the mir-612 gene; however, we found no significant association between the rs12803915 polymorphism and ALL risk.

DNA methyltransferase3A (DNMT3A) is necessary for the adjustment of gene expression, and the mutations in the DNMT3A gene are reported in a variety of leukemia cases. DNMT3A mutations are during cancer progression and cause poor prognosis in many leukemias. Thus, this gene can be a target for new treatments. This study aimed to examine the distribution of DNMT3A mutations in Iranian acute leukemia patients.

In this study, diagnostic samples from 45 patients with de novo acute leukemia, including 22 acute myeloid leukemia (AML) patients, and 23 acute leukemia lymphoblastic (ALL) patients were screened, from April 2017 to March 2018 for the incidence of DNMT3A mutations by polymerase chain reaction and direct sequencing.

A total of 2 (9.1%) AML cases and 1 (4.34%) ALL cases were found to have the DNMT3A R882H mutation. It was found that a total of 22.7% and 21.7% of patients with AML and ALL had polymorphism rs368516543, respectively. DNMT3A mutations were considerably associated with higher age in AML patients.

The findings suggest that the DNMT3A mutations are probably a new biomarker in the early examination and treatment of acute leukemia, even though further studies are needed.

Primary amenorrhea refers to the absence of menstruation in females of reproductive by age 16 when the development of secondary sexual characteristics is evident (breast development, pubic hair) or by age 14 when there are no secondary sexual characteristics are present. Primary amenorrhea can occur in several quite different reasons. Common hormonal causes of primary amenorrhea include constitutional delay, hypothalamic or pituitary disorders, chronic systemic disease, and primary ovarian insufficiency, some endocrine gland disorders, and other causes. Previous studies suggested that chromosomal abnormality is the second most common cause of amenorrhea. This report aims to measure the prevalence of the chromosomal abnormality in primary amenorrhea (PA) patients in the northeast of Iran.

Chromosomal study was carried out on 200 patients with clinical features. The standard method for culturing peripheral venous blood lymphocyte was to prepare metaphase chromosomes and perform routine GTG band analysis.

The results revealed that 71% of PA had normal female karyotype (46,XX) and 29% showed different chromosomal abnormalities. The chromosomal abnormalities can be categorized into seven primary groups with or without mosaicism. 1- The most common karyotype was X chromosome aneuploidy (10.5%, n=21), 2- Male karyotype with or without structural abnormality of Y chromosome (5.5 %, n=11), 3- Mosaicism of turner karyotype and structural anomalies of X chromosome (4%, n=8), 4- Structural anomalies of the X chromosome (3.5%, n=7), 5- Mosaicism of turner karyotype and normal karyotype (3%, n=6), 6- Mosaicism of turner karyotype and male karyotype (1.5%, n=3) and 7- Super female karyotype (1%, n=2).

The present study has emphasized that early cytogenetic and timely investigation can be necessary for the evaluation of primary amenorrhea.

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). 

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.

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).

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.

Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML).  Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran.

Survival rates of 42 APL patients with t(15;17)(q22;q12) were assessed. Clinical information was obtained from archived medical records. Statistical analysis was performed by SPSS 18 software using log-ranked test and Kaplan Maier survival analysis.

Females and males comprised 49% and 51%, respectively. The mean age at diagnosis was 34.3 14.1 years old. During the study period, 17 demises occurred in males, while this number was 7 in females. The mean survival of patients (month) was 23.22 3.57 (95% CI: 16.21 30.2).  The five-year survival rate obtained 30%. Regarding demographic and clinical features, the highest rates of 5-year survival were recorded in patients with 20-35 years old (47.6%), males (51%), white blood cell count 140 /l (100%).

Younger age, lower WBC count and higher platelet count were significantly associated with longer survival in AML patients with t(15;17)(q22; q12).

Idiopathic pulmonary fibrosis (IPF) is a chronic and uniformly fatal interstitial lung disease with incompletely understood pathogenesis. Several studies have given the evidence for and against viral cofactors in the pathogenesis of Idiopathic pulmonary fibrosis. In this study Epstein-Bar Virus (EBV) and Human Herpesvirus 8 (HHV-8) have been studied for a possible role in the pathogenesis of IPF.

Polymerase chain reaction (PCR) was employed for the detection of EBV and HHV-8 in 58 formalin-fixed paraffin-embedded lung tissue specimens (29 controls and 29 IPF specimens).

EBV DNA was present in the lung tissue of 6 out of 29 (20.7%) IPF specimens compared with 1 out of 29 (3.4%) controls (P=0.102). The HHV-8 gene was identified in 3 out of 29 (10.3%) cases of IPF specimens. The control group showed no evidence of HHV-8 gene (P=0.227).

Although multiple studies are strongly suggestive of a role for EBV and HHV-8 in the development of IPF, there was no statistically significant difference in the prevalence of EBV and HHV-8 DNA in the IPF specimens and controls in this study.

Excess proliferation of blood cells may lead to leukemia, which is associated with structural and numerical chromosomal aberrations. Cytogenetic findings of acute lymphoblastic leukemia can be applicable in diagnosis, prognosis, and treatment selection for patients. In the present study we have evaluated molecular, cytogenetic, and immunophenotypic findings in acute lymphoblastic leukemia patients from Mashhad, a city in Northeast Iran.
This cross-sectional study enrolled 124 patients with acute lymphoblastic leukemia during 2015-2017. Two expert hematopathologists confirmed the diagnosis of acute lymphoblastic leukemia in patients’ peripheral blood and bone marrow smears. Molecular tests that included t(4;11), t (1;19), t (9;22)-190, and t (12;21) were done by reverse transcriptase real-time quantitative PCR. We performed karyotyping and immunophenotyping of the bone marrow samples. The data were analyzed by SPSS v.17.
Mean age of studied cases was 20.01 years. Participants consisted of 64% males and 36% females. Cytogenetic results showed that 23.37% of participants had a normal karyotype; the other participants had the following abnormalities: hyperdiploidy (12.06%), hypodiploidy (21.55%), pseudodiploidy (24.13%), and high hyperdiploidy (18.10%). Molecular analysis of karyotype patterns indicated that 14% of the acute lymphoblastic leukemia patients had the t(12;21), 9% with t(1;19), 2.5% with t(4;11), and 2.5% had the t(9;22).
The unique findings of the present study were the presence of previously unreported novel abnormalities. These findings might be useful for oncologists and hematologists in predicting outcome, remission, survival, and treatment response in acute lymphoblastic leukemia patients.