Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.

Small molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the kinase and inhibit downstream signaling pathways.

Performance Evaluation of a New Fluorescent-Based Lateral Flow Immunoassay for Quantification of Hemoglobin A1c (HBA1c) in Diabetic Patients.

Background: Rapid hemoglobin A1C (HbA1c) level monitoring is essential in slowing the progression of diabetes. This need becomes challenging in low resources countries where the social burden of the disease is overwhelming. Recently, fluorescent-based lateral flow immunoassays (LFIAs) gained wide attention for small laboratories and population surveillance.

Gene Expression Landscape of Chronic Myeloid Leukemia K562 Cells Overexpressing the Tumor Suppressor Gene PTPRG.

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML.

Assessment of the Neutralizing Antibody Response of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Naïve and Previously Infected Individuals: A Comparative Study.

The currently authorized mRNA COVID-19 vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, offer great promise for reducing the spread of the COVID-19 by generating protective immunity against SARS-CoV-2. Recently, it was shown that the magnitude of the neutralizing antibody (NAbs) response correlates with the degree of protection. However, the difference between the immune response in naïve mRNA-vaccinated and previously infected (PI) individuals is not well studied.

Description of PTPRG genetic variants identified in a cohort of Chronic Myeloid Leukemia patients and their ability to influence response to Tyrosine kinase Inhibitors.

Tyrosine kinase inhibitors (TKIs) have remarkably transformed Ph+ chronic myeloid leukemia (CML) management; however, TKI resistance remains a major clinical challenge. Mutations in BCR-ABL1 are well studied but fail to explain 20-40% of resistant cases, suggesting the activation of alternative, BCR-ABL1-independent pathways. Protein Tyrosine Phosphatase Receptor Gamma (PTPRG), a tumor suppressor, was found to be well expressed in CML patients responsive to TKIs and remained at low level in resistant patients.

Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naïve and previously infected individuals.

Background: Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, obtained the Emergency Use Listing by WHO for preventing COVID-19. However, little is known about the difference in antibody responses induced by these two mRNA vaccines in naïve and previously infected (PI) individuals.

Method: We investigated the levels of anti-S-RBD (total, IgG and IgA) levels in naïve and PI individuals, 1-13 (median = 6) weeks following the second dose of either vaccine.

Incidence, risk factors, and feto-maternal outcomes of inappropriate birth weight for gestational age among singleton live births in Qatar: A population-based study.

Background: Abnormal fetal growth can be associated with factors during pregnancy and at postpartum.

Objective: In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants.

Methods: We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar.

Incidence, Risk Factors, and Outcomes of Preterm and Early Term Births: A Population-Based Register Study.

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar.

Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients.

Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (CML). In addition, the BCR-ABL1 transcript level is currently a key predictive biomarker of CML response to treatment with Tyrosine Kinase Inhibitors (TKIs).

The impact of size on particle drainage dynamics and antibody response.

Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B cells and innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T = 3 icosahedral particles.

Shaping Modern Vaccines: Adjuvant Systems Using MicroCrystalline Tyrosine (MCT).

The concept of adjuvants or adjuvant systems, used in vaccines, exploit evolutionary relationships associated with how the immune system may initially respond to a foreign antigen or pathogen, thus mimicking natural exposure. This is particularly relevant during the non-specific innate stage of the immune response; as such, the quality of this response may dictate specific adaptive responses and conferred memory/protection to that specific antigen or pathogen. Therefore, adjuvants may optimise this response in the most appropriate way for a specific disease.

Children's prolonged exposure to the toxic stress of war trauma in the Middle East.

Conflict leads to toxic stress and health problems in childhood and beyond. Long term investment in evidence informed mitigation strategies is needed to end the devastating cycles of violence, write

Aberrant DNA methylation of PTPRG as one possible mechanism of its under-expression in CML patients in the State of Qatar.

Background: Several studies showed that aberrant DNA methylation is involved in leukemia and cancer pathogenesis. Protein tyrosine phosphatase receptor gamma (PTPRG) expression is a natural inhibitory mechanism that is downregulated in chronic myeloid leukemia (CML) disease. The mechanism behind its downregulation has not been fully elucidated yet.

The 3Ds in virus-like particle based-vaccines: "Design, Delivery and Dynamics".

Vaccines need to be rationally designed in order be delivered to the immune system for maximizing induction of dynamic immune responses. Virus-like particles (VLPs) are ideal platforms for such 3D vaccines, as they allow the display of complex and native antigens in a highly repetitive form on their surface and can easily reach lymphoid organs in intact form for optimal activation of B and T cells. Adjusting size and zeta potential may allow investigators to further fine-tune delivery to lymphoid organs.

Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia.

Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. β-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between β-catenin and PTPRG in CML cells.

New Horizons for Molecular Genetics Diagnostic and Research in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a highly heritable, heterogeneous, and complex pervasive neurodevelopmental disorder (PND) characterized by distinctive abnormalities of human cognitive functions, social interaction, and speech development.Nowadays, several genetic changes including chromosome abnormalities, genetic variations, transcriptional epigenetics, and noncoding RNA have been identified in ASD. However, the association between these genetic modifications and ASDs has not been confirmed yet.

Overview and Introduction to Autism Spectrum Disorder (ASD).

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder generally manifesting in the first few years of life and tending to persist into adolescence and adulthood. It is characterized by deficits in communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities. It is a disorder with multifactorial etiology.

Virus-like particles for vaccination against cancer.

Active immunotherapy of cancer aims to treat the disease by inducing effective cellular and humoral immune responses. Virus-like particle-based vaccines have evolved dramatically over the last few decades, greatly reducing morbidity and mortality of several infectious diseases and expectedly preventing cervical cancer caused by human papilloma virus. In contrast to these broad successes of disease prevention, therapeutic cancer vaccines remain to demonstrate clinical benefit.

Circulating microparticles as biomarkers of stroke: A focus on the value of endothelial- and platelet-derived microparticles.

Stroke is one of the leading causes of mortality and disability worldwide. Numerous pathophysiological mechanisms involving blood vessels, coagulation and inflammation contribute to the vascular occlusion. Perturbations in these pathways can be detected by numerous methods including changes in endoplasmic membrane remodeling and rearrangement leading to the shedding of microparticles (MPs) from various cellular origins in the blood.

A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients.

Background: Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands in the promoter region. Although a critical role in human hematopoiesis and an oncosuppressor role in chronic myeloid leukemia (CML) have been reported, only one polyclonal antibody (named chPTPRG) has been described as capable of recognizing the native antigen of this phosphatase by flow cytometry. Protein biomarkers of CML have not yet found applications in the clinic, and in this study, we have analyzed a group of newly diagnosed CML patients before and after treatment.

Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

Background: Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail.

Aim: This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study.

Methods: This is a follow-up study of a new cohort of CML patients.

Genetics of human isolated hereditary nail disorders.

Human hereditary nail disorders constitute a rare and heterogeneous group of ectodermal dysplasias. They occur as isolated and/or syndromic ectodermal conditions where other ectodermal appendages are also involved, and can occur associated with skeletal dysplasia. 'Nail disorder, nonsyndromic congenital' (OMIM; Online Mendelian Inheritance in Man) is subclassified into 10 different types.