zahra khoshnegah

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.

platelet count errors such as PU flag, could cause misdiagnosis.

Case report:

 a 36-year-old thalassemia minor male with fever and myalgia presented. Petechiae and purpura in the lower extremities of patients were observed in physical examination. The platelet count was assessed by Nihon Kohden’s Celltac G cell and Sysmex XP-300 cell counter and the platelet count was reported 10,000/μL and 129,000/μL respectively. But peripheral blood smear assessment confirms that the result of the Sysmex XP-300 cell counter was wrong and a platelet flag was seen. This situation can be corrected by the CBC histogram and peripheral blood smear evaluation.

Sysmex XP-300 cell counter inability to differentiate severely microcytic cells from platelets can cause the PU error, which means the severe microcytic RBCs were counted as platelets that cause the platelet count falsely higher than the actual number in this patient. The PU flag means the platelet histogram intersects the PU line and does not touch the zero baseline, that occur in conditions such as platelet clumps, giant platelet, microcytic and fragmented or dysplastic RBCs in hemolytic anemia. In Nihon Kohden’s Celltac G cell counter, due to the change in the PU line this error was prevented and the actual platelet count of the patient was reported. By the way, to avoid such errors, abnormal platelet counts should always be confirmed with the findings of PBS. ConclusionPoikilocytosis such as microcytic RBCs can cause the PU flag, so platelet and erythrocytes histograms and PBS evaluation should be assessed.

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.

autoantibodies, which results in Ethylenediaminetetraacetic Acid (EDTA) independent pseudo thrombocytopenia (PTCP). Its diagnosis is made based on the peripheral blood smear (PBS) examination and pre-test warming blood sample. Here, a case of PTCP secondary to PCA is presented. He was first admitted for pre-surgical tests but his platelet count was low. His blood was taken with EDTA and sodium citrate anticoagulant to rule pre-analytical error out. Then his sample warmed up and the test was run again with Mindray BC-6000 automated cell counter. Moreover, the rheumatologic tests were done for him. His platelet count was 23×109/L at first, and PBS showed many platelet aggregates. The low platelet count was not correct with Sodium Citrate or re-sampling with EDTA so platelet satellitism and improper sampling were ruled out. By warming the sample up to 37⸰C, the Platelet count rose to 216×109 / L.  The rheumatologic tests were negative except for HLA-B27 which was positive. Finally, he was diagnosed with PCA which is due to a cold antibody (clinically insignificant). This diagnosis is important for the prevention of recurrent tests, unnecessary platelet transfusion, and other problems. Here these conditions will be discussed.

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.

 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.

 COVID-19 has enforced high burden on health systems universally. To better allocate limited health equipment, we aimed to investigate the prognostic impacts of laboratory parameters.

 All SARS-CoV-2 patients admitted to Imam-Reza University Hospital, Mashhad, Iran, during three COVID19 peak periods in Iran (March to April 2020, July to August, and October to November 2020) were enrolled the study. Demographic and laboratory data were extracted and compared between survivors and non-survivors. Regression analyses and receiver operating characteristic (ROC curve) were used to identify risk factors and assess the ability of laboratory tests in predicting in-hospital mortality.

 A total of 2156 COVID19 patients were included in the analysis, with a mean age of 60.20 (±18.8) years. Most patients were male (57%). Multiple regression analysis identified older age (OR=1.01), male sex (OR=2.34), lymphopenia (OR=2.12), LDH >500U/L (OR=2.17), hypernatremia (OR=9.7), urea >45mg/dL (OR=3.6), and BS >200mg/dl (OR=1.93) as significant risk factors for in-hospital death. Using ROC curve analysis, D-dimer (>1000ng/ml) as well as CK-Mb (>28U/L) both with sensitivities and specificities of more than 80% and PPV of about 90% were able to identify patients with higher possibility of in-hospital death.

 Male sex, older age, lymphopenia, hypernatremia, increased Urea, increased LDH, and hyperglycemia may serve as potential risk factors for in-hospital death. D-dimer and CK-MB may be used in identifying patients with high probability of in-hospital death. These tests may be used in clinical decision-making in order to improve outcomes of patients with COVID-19.

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.