Genomics of Acute Myeloid Leukemia

Acute myelogenous leukemia (AML) is a clonal, malignant disease of hematopoietic tissue that is characterized by accumulation of abnormal (leukemic) blast cells, principally in the bone marrow. Representation of these genetic mutations and the involvement patterns seems to follow specific and temporally ordered fluctuating manners. Somatic mutations in these genes are represented as a variety of recurrent chromosomal abnormalities, e.g., t (8;21), t(15;17), etc., or by the presence of prognostic markers, e.g., FLT3, MLL, NPM1 and CEBPA as well as encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such genomic changes may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. Majority of genetic data are now being used to classification, risk stratification, and clinical care of patients. The unprecedented molecular characterization provided by advanced and deeply sensitized molecular assays like next-generation sequencing (NGS) offers the potential for an individualized approach to treatment in AML, bringing us one step closer to personalized medicine

Remembering the Bengali contribution during the First World War

The First World War seems to be part of a distant past for most Bengalis, with the new generation of UK's Bengali diaspora being left out of the nation's collective memorialisation. A more inclusive remembrance of the First World War is required to address this, writes Ansar Ahmed Ullah, who recalls Bengal's contribution during World War One

Assessment of WT1 expression as a marker of treatment outcome in karyotype normal acute myeloid leukemia patients in Pakistan

Currently, there is an effort to predict relapse by follow-up monitoring of MRD and subsequently to begin the treatment of the patients during their clinical and hematological remission prior to overt hematological relapse. Expression of WT1 in AM Lis known to be independently associated with significant inferior response to therapy and short survival outcome. Follow-up monitoring of WT1 gene expression during or after therapy would be a valuable predictive marker for early recurrence or relapse of AMLdisease. This pilot study evaluated newly diagnosed and post-induction or consolidation chemotherapy of AMLpatients who were registered with the Oncology Clinics of the Aga Khan University Hospital, Karachi. High WT1 burden (\u3e 5000 copies/ml) in 2 patients was indicative of early recurrence of the disease along with shorter disease-free and overall survival. Low WT1 expression (\u3c 200 copies/ml) in 2 patients after induction and consolidation therapy, respectively, was suggestive of better prognosis

A cross sectional evaluation of the corona-score for swift identification of SARS-CoV-2 infection at a tertiary care hospital in Pakistan

Background: The Corona-Score is one of the first and most widely used predictive model for coronavirus 2 (SARS-CoV-2) infection. The purpose of this study was to validate the performance of Corona-Score in a cohort of Pakistani patients pursuing care for suspected infection.Methods: After seeking institution\u27s ethical committee exemption, results of serum lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, absolute lymphocyte and neutrophil counts, chest x-ray findings and demographics of suspected COVID-19 cases with respiratory symptoms were recouped from electronic medical record. The pre-validated score as proposed by Kurstjens S et al., was calculated. The subjects were divided into SARS-CoV-2 positive and negative on the basis of reverse transcription-polymerase chain reaction (RT-PCR) findings. Median and interquartile range (IQR) was calculated for the score in the two groups and the difference was assessed using the independent sample median test. Receiver operating characteristics (ROC) curve analysis was plotted. Statistical analyses were carried out using SPSS 26, with statistical significance set at p value \u3c 0.05.Results: A total of sixty cases, 30 (50%) RT-PCR positive and 30 (50%) negative with a median Corona-Score of 3.5 (IQR: 0-6) and 1.5 (IQR: 0-4) respectively, were evaluated. A p-value of 0.61 showing no statistically significant between group differences was observed. The area under the curve of Corona-Score in our population of patients was 0.59 (95% CI: 0.45-0.74). Using the cut-off values of four originally identified by Kurstjens et al. the model displayed 43.3% sensitivity and 70% specificity with an overall accuracy of 56.67%.Conclusion: Corona-Score displayed a lower diagnostic accuracy which may be attributable to the different genetic framework, viral strain and severity of the disease in Pakistanis compared to the population where this score was originally validated. However, large multi-center studies across the country are dire need of time to evaluate the score in overly exhausted health care setup and limited availability of PCR testing

Evaluation of serum ferritin for prediction of severity and mortality in COVID-19- A cross sectional study

Background: Ferritin even though widely recognized as a representative of total body iron stores, its prognostic utility is linked with COVID-19. This study was aimed at evaluation of the association of ferritin with severity in Coronavirus disease 2019 (COVID-19), hospitalized patients and to test the hypothesis that it is an independent predictor of mortality.Material and methods: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi. Medical records of all in-patients including both genders, and all age groups with documented COVID-19 from 1st March to 10th August 2020 were reviewed. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. The details were recorded on a pre-structured performa. Between-group differences were tested using the Mann-Whitney\u27s U-test. The receiver operating characteristic curve was plotted for ferritin with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analyzed using Statistical Package for the Social Sciences (SPSS).Results: A total of 336 in patients were reviewed as declared COVID-19 positive during the study duration, and 157 were included in the final analysis including 108 males and 49 females. Statistically significant difference in ferritin was found in the two categories based on severity and mortality. Binary logistic regression showed ferritin to be an independent predictor of all-cause mortality supplemented with an AUC of 0.69 on ROC analysis.Conclusions: Serum ferritin concentration is a promising predictor of mortality in COVID-19 cases

Acute High Dose Reprotoxic Effects of Bisphenol-A on the Testicles of Adult Rodents.

Objectives: To evaluate the acute effects of high dose of bisphenol-A (BPA) induced in the testicles of adult rats.Methodology: An Experimental study was conducted at Anatomy Department, University of Health Sciences, Lahore, from January 2015 to December 2015.Twelve adult Wistar albino rats were weighed and divided into three groups of four rats each. Group A (control) was given corn oil (2ml/kg/day). Group B (BPA-100) was given BPA 100mg/kg/day dissolved in corn oil (2ml/kg/day). Group C (BPA-200) was given BPA 200mg/kg/day dissolved in corn oil (2ml/kg/day). The animals were sacrificed on the 8th day after weighing. Testis were weighed and fixed in Buoin’s solution. Johnson scoring was done in H&E stained slides. Basement membrane integrity was observed in PAS stained slides.Results: Group A rats showed normal parameters. Group B (BPA-100) showed a significant decrease in Johnson score and an increase in basement membrane disruption while the changes in body weight of animals and paired weight of testis was statistically insignificant. Group C (BPA 200) rats died within 3-4 days and the experiment was limited to two groups.Conclusion: The results of the present study indicate that a high dosage of Bisphenol A in rats causes significant disruption of the testicular histology and proves to be a significant reprotoxin even with a short duration of exposure