Global Globin Network and adopting genomic variant database requirements for thalassemia.

Thalassemia is one of the most prevalent monogenic disorders in low- and middle-income countries (LMICs). There are an estimated 270 million carriers of hemoglobinopathies (abnormal hemoglobins and/or thalassemia) worldwide, necessitating global methods and solutions for effective and optimal therapy. LMICs are disproportionately impacted by thalassemia, and due to disparities in genomics awareness and diagnostic resources, certain LMICs lag behind high-income countries (HICs).

Rare coinheritance of hemoglobin vancleave with severe beta-thalassemia mutation in a patient with secondary erythrocytosis.

Hemoglobin (Hb) Vancleave (NM_000518.5:c.431 A > T; dbSNP: rs33918338) is an extremely rare structural hemoglobin variant worldwide, and studies are limited.

Mutation analysis of BCR-ABL1 kinase domain in chronic myeloid leukemia patients with tyrosine kinase inhibitors resistance: a Malaysian cohort study.

Objective: Mutational analysis of BCR::ABL1 kinase domain (KD) is a crucial component of clinical decision algorithms for chronic myeloid leukemia (CML) patients with failure or warning responses to tyrosine kinase inhibitor (TKI) therapy. This study aimed to detect BCR::ABL1 KD mutations in CML patients with treatment resistance and assess the concordance between NGS (next generation sequencing) and Sanger sequencing (SS) in detecting these mutations.

Results: In total, 12 different BCR::ABL1 KD mutations were identified by SS in 22.

Clinical and haematological characteristics of 38 individuals with Hb G-Makassar in Malaysia.

Haemoglobin (Hb) G-Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high-performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the β-globin () gene with different pathogenicities.

Characterization of New Alpha Zero (α) Thalassaemia Deletion (--) among Malays in Malaysian Population.

Malaysia is a multicultural and multiethnic country comprising numerous ethnic groups. From the total population of 32.7 million, Malays form the bulk of the Bumiputera in Malaysia comprise about 69.

Molecular genetic aberrations in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is the second most common form of blood cancer characterized by clonal expansion of malignant plasma cells within the bone marrow. MM is a complex, progressive, and highly heterogeneous malignancy, which occurs via a multistep transformation process involving primary and secondary oncogenic events. Recent advances in molecular techniques have further expanded our understanding of the mutational landscape, clonal composition, and dynamic evolution patterns of MM.

Systematic review and meta-analysis of mesenchymal stromal/stem cells as strategical means for the treatment of COVID-19.

Background: In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions.

Gene Mutation Spectrum among Alpha-Thalassaemia Patients in Northeast Peninsular Malaysia.

(1) Background: Alpha (α)-thalassaemia is a genetic disorder that affects 5% of the world population. Deletional or nondeletional mutations of one or both and on chromosome 16 will result in reduced production of α-globin chains, a component of haemoglobin (Hb) that is required for the formation of red blood cells (RBCs). This study aimed to determine the prevalence, haematological and molecular characterisations of α-thalassaemia.

Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) for the Diagnosis of Thalassemia.

Thalassemia is one of the most heterogeneous diseases, with more than a thousand mutation types recorded worldwide. Molecular diagnosis of thalassemia by conventional PCR-based DNA analysis is time- and resource-consuming owing to the phenotype variability, disease complexity, and molecular diagnostic test limitations. Moreover, genetic counseling must be backed-up by an extensive diagnosis of the thalassemia-causing phenotype and the possible genetic modifiers.

Molecular and hematological studies in a cohort of beta zero South East Asia deletion (β°-thal SEA) from Malaysian perspective.

Abstract: We report the haematological parameters and molecular characterization of beta zero (β°) South East Asia (SEA) deletion in the gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (β°)-thalassaemia.

Methods: Retrospective study on 17 cases of (β°) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated.

Neuroprotective effect of phospholipase A from Malaysian venom against HO-induced cell damage and apoptosis.

Oxidative stress is one of the factors involved in the pathogenesis of several neurodegenerative diseases. It has been reported that a secretory phospholipase A known as A2-EPTX-NSm1a has lower cytotoxicity in neuronal cells compared to its crude venom. In this study, A2-EPTX-NSm1a was tested for its neuroprotective activity on human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons against oxidative stress induced by hydrogen peroxide (HO).

Gene expression profiling and in vitro functional studies reveal RAD54L as a potential therapeutic target in multiple myeloma.

Background: Current advances in the molecular biology of multiple myeloma (MM) are not sufficient to fully delineate the genesis and development of this disease.

Objective: This study aimed to identify molecular targets underlying MM pathogenesis.

Methods: mRNA expression profiling for 29 samples (19 MM samples, 7 MM cell lines and 3 controls) were obtained using microarray.

Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries.

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies.

Comprehensive analysis of mutations and clonal evolution patterns in a cohort of patients with cytogenetically normal acute myeloid leukemia.

Background: Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability, clonal selection and evolution of leukemic clones during treatment. We performed high throughput exome sequencing of matched presentation and relapsed samples from 6 cytogenetically normal AML (CN-AML) patients treated with standard remission induction chemotherapy in order to contribute with the investigation of the mutational landscape of CN-AML and clonal evolution during AML treatment.

Result: A total of 24 and 32 somatic variants were identified in presentation and relapse samples respectively with an average of 4.

Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population.

This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.

Construction of a microRNA-mRNA Regulatory Network in Cytogenetically Normal Acute Myeloid Leukemia Patients.

The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of CN-AML.

Identification of FLT3 and NPM1 Mutations in Patients with Acute Myeloid Leukaemia.

Objective: The most frequent acquired molecular abnormalities and important prognostic indicators in patients with Acute Myeloid Leukaemia (AML) are fms-like tyrosine kinase-3 gene (FLT3) and nucleophosmin-1 (NPM1) mutations. Our study aims to develop a cost effective and comprehensive in-house conventional PCR method for detection of FLT3-ITD, FLT3-D835 and NPM1 mutations and to evaluate the frequency of these mutations in patients with cytogenetically normal (CN) AML in our population. Methods: A total of 199 samples from AML patients (95 women, 104 men) were included in the study.

Circulating cytokines and small molecules follow distinct expression patterns in acute myeloid leukaemia.

Background: Although aberrant expression of cytokines and small molecules (analytes) is well documented in acute myeloid leukaemia (AML), their co-expression patterns are not yet identified. In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML.

Methods: We used multiplex array technology to simultaneously detect and quantify 32 plasma analyte (22 reported analytes and 10 novel analytes) levels in 38 patients.

Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases.

Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the ETV6/RUNX1 fusion gene using whole-exome sequencing.

Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization.

Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients.