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Fulltext Hemorrhage in a Fetal Ovarian Cyst

Hassan R, Chong YC, Khairun Nisa M, Yew CG, Tan PG, Mazlin J

J Neonatal Surg, 2017 Apr 15;6(2):49.
PMID: 28770146 DOI: 10.21699/jns.v6i2.505
Fulltext Continental Shelf Sediments of Sarawak, Malaysian Borneo

Morni WZW, Ab Rahim SAK, Masron T, Rumpet R, Musel J, Hassan R

ScientificWorldJournal, 2017;2017:4853048.
PMID: 29075660 DOI: 10.1155/2017/4853048

Sediment distributions in deep sea influence the benthic community structure and thus play an important role in shaping the marine ecosystem. Several studies on sediment characteristics had been conducted in South China Sea (SCS), but only limited to coastal areas of regions within SCS territories. Therefore, this study was carried out to analyze the benthic sediment profile in an area beyond 12 nautical miles off the coast of Sarawak, southern SCS. Sediment samples were collected from 31 stations, comprising three depth ranges: (I) 20-50 m, (II) 50-100 m, and (III) 100-200 m. The total organic matter (TOM) contents were determined and subjected to dry and wet sieving methods for particle size analysis. TOM contents in the deep area (>50 m) were significantly higher (p = 0.05) and positively correlated (r = 0.73) with silt-clay fraction. About 55% and 82% of stations in strata II and III, respectively, were dominated by silt-clay fractions (<63 μm mean diameter), coherent with TOM data. In addition, sediments in the deep area (>50 m) tend to be poorly sorted, very fine skewed, and platykurtic. Unlike data obtained 20 years ago which reported high content of silt-clay (58%), this study recorded a lower content (35%); therefore, changes in sediment load had been observed in southern SCS.
Fulltext Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing

Ambayya A, Razali R, Sulong S, Zulkefli ES, Yap YY, Sathar J, et al.

Cancers (Basel), 2023 Feb 22;15(5).
PMID: 36900179 DOI: 10.3390/cancers15051386

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients' samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.
Prevalence and Distribution of Major β-Thalassemia Mutations and HbE/β-Thalassemia Variant in Nepalese Ethnic Groups

Lama R, Yusof W, Shrestha TR, Hanafi S, Bhattarai M, Hassan R, et al.

Hematol Oncol Stem Cell Ther, 2022 Mar 01;15(1):279-284.
PMID: 33592169 DOI: 10.1016/j.hemonc.2021.01.004

BACKGROUND: Beta-thalassemia is a genetic disorder that is inherited in an autosomal recessive pattern. This genetic disease leads to a defective beta-globin hemoglobin chain causing partial or complete beta-globin chain synthesis loss. Beta-thalassemia major patients need a continuous blood transfusion and iron chelation to maintain the normal homeostasis of red blood cells (RBCs) and other systems in the body. Patients also require treatment procedures that are costly and tedious, resulting in a serious health burden for developing nations such as Nepal.
METHODS: A total of 61 individuals clinically diagnosed to have thalassemia were genotyped with multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Twenty-one major mutations were investigated using allele-specific primers grouped into six different panels.
RESULTS: The most common mutations found (23%) were IVS 1-5 (G-C) and Cd 26 (G-A) (HbE), followed by 619 deletion, Cd 8/9 (+G), Cd 16 (-C), Cd 41/42 (-TTCT), IVS 1-1 (G-T), Cd 19 (A-G), and Cd 17 (A-T) at 20%, 12%, 8%, 6%, 4%, 3%, and 1%, respectively.
CONCLUSION: The results of this study revealed that Nepal's mutational profile is comparable to that of its neighboring countries, such as India and Myanmar. This study also showed that thalassemia could be detected across 17 Nepal's ethnic groups, especially those whose ancestors originated from India and Central Asia.
Fulltext Anti-D Alloimmunization Following Rhesus-Incompatible Platelet Transfusion in a Myelodysplastic Syndrome Patient

Hanafi R, Zulkeflee RH, Hassan MN, Saidin NIS, Adzahar S, Hassan R

Cureus, 2024 Mar;16(3):e57165.
PMID: 38681415 DOI: 10.7759/cureus.57165

Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh) incompatibility between donors and recipients during platelet transfusions, is heightened, especially with whole blood-derived pooled platelets as opposed to apheresis platelets. Although the occurrence of alloimmunization from platelet transfusions is minimal, there is an ongoing debate about whether Rh immune globulin (RhIg) should be administered to Rhesus D (RhD)-negative recipients of RhD-positive platelet units. We present a unique case of anti-D alloimmunization in a 56-year-old patient with underlying MDS following multiple platelet transfusions but never received packed cell transfusion or anti-D immunoglobulin. Some studies advocate for RhIg administration in specific scenarios and for certain patient populations. This case underscores the importance of considering Rhesus compatibility or administering anti-D immunoglobulin in cases where frequent platelet transfusions are required.
Fulltext Graph-based extractive text summarization method for Hausa text

Bichi AA, Samsudin R, Hassan R, Hasan LRA, Ado Rogo A

PLoS One, 2023;18(5):e0285376.
PMID: 37159449 DOI: 10.1371/journal.pone.0285376

Automatic text summarization is one of the most promising solutions to the ever-growing challenges of textual data as it produces a shorter version of the original document with fewer bytes, but the same information as the original document. Despite the advancements in automatic text summarization research, research involving the development of automatic text summarization methods for documents written in Hausa, a Chadic language widely spoken in West Africa by approximately 150,000,000 people as either their first or second language, is still in early stages of development. This study proposes a novel graph-based extractive single-document summarization method for Hausa text by modifying the existing PageRank algorithm using the normalized common bigrams count between adjacent sentences as the initial vertex score. The proposed method is evaluated using a primarily collected Hausa summarization evaluation dataset comprising of 113 Hausa news articles on ROUGE evaluation toolkits. The proposed approach outperformed the standard methods using the same datasets. It outperformed the TextRank method by 2.1%, LexRank by 12.3%, centroid-based method by 19.5%, and BM25 method by 17.4%.
Fulltext The Prevalence of TET2 Gene Mutations in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis

Chia YC, Islam MA, Hider P, Woon PY, Johan MF, Hassan R, et al.

Cancers (Basel), 2021 Jun 20;13(12).
PMID: 34203097 DOI: 10.3390/cancers13123078

Multiple recurrent somatic mutations have recently been identified in association with myeloproliferative neoplasms (MPN). This meta-analysis aims to assess the pooled prevalence of TET2 gene mutations among patients with MPN. Six databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science and Embase) were searched for relevant studies from inception till September 2020, without language restrictions. The eligibility criteria included BCR-ABL-negative MPN adults with TET2 gene mutations. A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses explored results among different continents and countries, WHO diagnostic criteria, screening methods and types of MF. Quality assessment was undertaken using the Joanna Briggs Institute critical appraisal tool. The study was registered with PROSPERO (CRD42020212223). Thirty-five studies were included (n = 5121, 47.1% female). Overall, the pooled prevalence of TET2 gene mutations in MPN patients was 15.5% (95% CI: 12.1-19.0%, I2 = 94%). Regional differences explained a substantial amount of heterogeneity. The prevalence of TET2 gene mutations among the three subtypes PV, ET and MF were 16.8%, 9.8% and 15.7%, respectively. The quality of the included studies was determined to be moderate-high among 83% of the included studies. Among patients with BCR-ABL-negative MPN, the overall prevalence of TET2 gene mutations was 15.5%.
Fulltext HDG-select: A novel GUI based application for gene selection and classification in high dimensional datasets

Hameed SS, Hassan R, Hassan WH, Muhammadsharif FF, Latiff LA

PLoS One, 2021;16(1):e0246039.
PMID: 33507983 DOI: 10.1371/journal.pone.0246039

The selection and classification of genes is essential for the identification of related genes to a specific disease. Developing a user-friendly application with combined statistical rigor and machine learning functionality to help the biomedical researchers and end users is of great importance. In this work, a novel stand-alone application, which is based on graphical user interface (GUI), is developed to perform the full functionality of gene selection and classification in high dimensional datasets. The so-called HDG-select application is validated on eleven high dimensional datasets of the format CSV and GEO soft. The proposed tool uses the efficient algorithm of combined filter-GBPSO-SVM and it was made freely available to users. It was found that the proposed HDG-select outperformed other tools reported in literature and presented a competitive performance, accessibility, and functionality.
Fulltext Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units

Ho SF, Tan SJ, Mazlan MZ, Iberahim S, Lee YX, Hassan R

Diagnostics (Basel), 2023 Jul 21;13(14).
PMID: 37510189 DOI: 10.3390/diagnostics13142445

Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.
Fulltext Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Zulkeflee RH, Zulkafli Z, Johan MF, Husin A, Islam MA, Hassan R

Int J Environ Res Public Health, 2021 Jul 16;18(14).
PMID: 34300032 DOI: 10.3390/ijerph18147582

Mutations of JAK2V617F, CALR, and MPL genes confirm the diagnosis of myeloproliferative neoplasm (MPN). This study aims to determine the genetic profile of JAK2V617F, CALR exon 9 Type 1 (52 bp deletion) and Type 2 (5 bp insertion), and MPL W515 L/K genes among Malaysian patients and correlate these mutations with clinical and hematologic parameters in MPN. Mutations of JAK2V617F, CALR, and MPL were analyzed in 159 Malaysian patients using allele-specific polymerase chain reaction, including 76 polycythemia vera (PV), 41 essential thrombocythemia (ET), and 42 primary myelofibrosis (PMF) mutations, and the demographics of the patients were retrieved. The result showed that 73.6% JAK2V617F, 5.66% CALR, and 27.7% were triple-negative mutations. No MPL W515L/K mutation was detected. In ET and PMF, the predominance type was the CALR Type 1 mutation. In JAK2V617F mutant patients, serum LDH was significantly higher in PMF compared to PV and ET. PV has a higher risk of evolving to post PV myelofibrosis compared to ET. A thrombotic event at initial diagnosis of 40.9% was high compared to global incidence. Only one PMF patient had a CALR mutation that transformed to acute myeloid leukemia. JAK2V617F and CALR mutations play an important role in diagnostics. Hence, every patient suspected of having a myeloproliferative neoplasm should be screened for these mutations.
Prevalence of GP. Mur variant phenotype among Malaysian blood donors

Hassan SN, Mohamad S, Kannan TP, Hassan R, Wei S, Wan Ab Rahman WS

Asian J Transfus Sci, 2023;17(2):169-174.
PMID: 38274953 DOI: 10.4103/ajts.ajts_125_21

BACKGROUND AND OBJECTIVE: A number of glycophorin variant phenotypes or hybrid glycophorin variants of the MNS blood group system bear multiple immunogenic antigens such as Mia, Mur, and MUT. In the East and Southeast Asian populations, glycoprotein (GP.) Mur is the most common glycophorin variant phenotype expressing those three immunogens. The aim of this study was to detect MNS system glycophorin variant phenotypes (GP. Mur, GP. Hop, GP. Bun, GP. HF, and GP. Hut) among Malaysian blood donors.
MATERIALS AND METHODS: In this cross-sectional study, 144 blood donors were selected under stratified random sampling. The deoxyribonucleic acid was extracted from whole blood samples, followed by a polymerase chain reaction assay. Sanger sequencing was used to identify the specific MNS variants and then validated by a serological crossmatch with known anti-Mur and anti-MUT.
RESULTS: GP. Mur was identified among Malaysian blood donors with a prevalence of 6.94%, and no other variants of the MNS system were found.
CONCLUSION: The present study substantiates that GP. Mur is the main variant of the MNS system glycophorin (B-A-B) hybrid in Malaysian blood donors. GP. Mur-negative red blood cells must therefore be considered in the current transfusion policy in order to prevent alloimmunization and immune-mediated transfusion reactions, particularly in transfusion-dependent patients.
Fulltext Falciparum Malaria Outbreak in Sabah Linked to an Immigrant Rubber Tapper

Jeffree SM, Ahmed K, Safian N, Hassan R, Mihat O, Lukman KA, et al.

Am J Trop Med Hyg, 2018 Jan;98(1):45-50.
PMID: 29141714 DOI: 10.4269/ajtmh.17-0081

Sabah is a Malaysian state situated in the northern part of Borneo, and it is endemic for malaria. The incidence of malaria is the lowest (0.05/1,000 population) in Penampang districts of Sabah. In June 26, 2012, two Plasmodium falciparum malaria cases were notified to public health department from a village in Penampang. Immediate investigation was initiated to identify the risk factors and to institute control measures. We performed active case finding by asking household members of all houses in the village regarding malaria symptoms and by examining blood smears. Environmental investigation was performed by collecting samples to detect mosquito breeding sites and to identify malaria transmitting vector mosquitoes. A case-control study with a ratio of 1:4 (11 cases and 44 controls) was conducted using self-administered questionnaire. The microscopic examination of blood smear for malarial parasite and entomology sampling was carried out. The malarial attack rate was 2.3%, 6/11 smears have gametocyte, and the case fatality rate was 9.1%. One case was a migrant rubber tapper from Indonesia which happened to be the first case with gametocyte positive. Overall, the incidence of malaria was higher (6/11) among rubber tappers. The odds of cases for those living nearby stagnant water were 7.3 [95% confidence interval: 1.2-43.5] times higher. In conclusion, an outbreak of P. falciparum malaria was introduced into a malaria-free village by a migrant rubber tapper, by whom the imported parasite was introduced to the community via vector Anopheles balabacensis. Living near stagnant water bodies was the risk factor in this outbreak.
Fulltext Randomized single-blinded study comparing sedation effectiveness and hemodynamic stability of remifentanil vs dexmedetomidine infusion for electrophysiology procedures in patients of National Heart Institute cathlab

Hassan R, Mutalib AA, Shang CY, Sachdev NS, Rahman FA, Ling ESL

J Interv Card Electrophysiol, 2024 Nov;67(8):1735-1743.
PMID: 39110272 DOI: 10.1007/s10840-024-01884-x

BACKGROUND: While studies comparing the effectiveness of remifentanil and dexmedetomidine are prevalent in other nations, using remifentanil alone is uncommon in Malaysia. This research aims to evaluate the effectiveness of sedation with remifentanil or dexmedetomidine infusion in monitored anesthesia care for electrophysiology procedures.
METHODS: This study is a single-center, single-blinded, prospective randomized clinical study. One hundred twenty patients were randomized into two groups (remifentanil vs dexmedetomidine). Demographic characteristics and clinical outcomes, including level of sedation, vital signs, and patient satisfaction were monitored and recorded.
RESULTS: Group R showed a higher mean observer's assessment of alertness/sedation score (3.9 ± 0.7 vs 3.6 ± 0.8; p = 0.008), mean arterial pressure (92.0 ± 12.0 vs 83.0 ± 13.0 mmHg; p
Towards understanding the role of nanomedicine in targeting TNFR2 in rheumatoid arthritis

Lambuk F, Nordin NA, Mussa A, Lambuk L, Ahmad S, Hassan R, et al.

Immunology, 2024 Dec;173(4):622-633.
PMID: 39191474 DOI: 10.1111/imm.13855

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium and progressive joint destruction which significantly affects both quality of life and socioeconomic status. Admittedly, various treatments are available, but they are usually accompanied by various side effects, from mild to severe, and potentially with adverse events. Tumour necrosis factor-alpha (TNF-α) plays a crucial role in the pathophysiology of RA. It promotes inflammatory, apoptosis and necroptosis via TNF receptor-1 (TNFR1) but elicit anti-inflammatory effects via TNFR2. Herein, targeting TNFR2 has gained attention in RA studies. Understanding the role of nanomedicine in modulating TNFR2 signalling may be the instrument in development of RA therapies. Nanotechnology has made a significant progress in treating various conditions of diseases since its inception. Due to this, nanomedicine has emerged as a promising therapeutics approach for RA. Recent studies have demonstrated the potential of nanomedicine in RA theranostics, combining therapy and diagnostics for improved treatment outcomes. Owing to the challenges and advancements in the field of nanotechnology, nanoparticles are seen as an applicable candidate in the treatment of RA. In this review, we provide an overview of the role of nanomedicine in targeting TNFR2 for the treatment of RA and highlight the limitations of current therapies as well as the potential of nanocarriers with controlled drug release and active targeting abilities.
Fulltext Classroom settings for visually impaired schoolchildren: A scoping review

Ahmad Najmee NA, Mohammed Z, Rahman MHA, Fadzil NM, Ludin AFM, Hassan R

PLoS One, 2025;20(2):e0318871.
PMID: 39977422 DOI: 10.1371/journal.pone.0318871

Visually impaired schoolchildren require classrooms tailored to their visual abilities and needs, as outlined in existing literature detailing optimal modifications, recommendations, and guidelines. The study aims to review existing literature on classroom modifications for visually impaired schoolchildren, outlining recommendations for creating ideal classrooms within mainstream physical settings. After initial screening, 712 publications (698 from databases and registers, and 14 from other methods) were identified for detailed review, of which 17 were ultimately eligible for inclusion. Through a systematic review of PubMed, Scopus, and Web of Science databases, along with additional sources up to February 2024, this research analyzed articles published from 1999 to 2024. A qualitative, thematic analysis was conducted on the included articles. Criteria included peer-reviewed journals, theses, and conference papers focusing on classroom settings for visually impaired schoolchildren aged 7 to 18. Key questions addressed are: 1) What classroom settings suit the needs of visually impaired schoolchildren? 2) What recommendations are tailored to visually impaired schoolchildren to create a conducive classroom environment? Analysis of 7 journal articles and 10 other publications revealed two main themes: optimizing classroom configuration and enhancing visual comfort. Articles primarily focused on suggestions for classroom layout, particularly furnishing arrangement (41%, n = 7) and enhancing lighting conditions (41% n = 7). However, concerns were raised about standard furniture designs and the need for tailored seating arrangements to meet the visual demands of visually impaired schoolchildren. Conclusion: This review provides valuable insights into creating optimal classroom settings for visually impaired schoolchildren, ensuring equal learning opportunities in a supportive environment tailored to their needs.
Federated learning for millimeter-wave spectrum in 6G networks: applications, challenges, way forward and open research issues

Qamar F, Kazmi SHA, Siddiqui MUA, Hassan R, Zainol Ariffin KA

PeerJ Comput Sci, 2024;10:e2360.
PMID: 39650377 DOI: 10.7717/peerj-cs.2360

The emergence of 6G networks promises ultra-high data rates and unprecedented connectivity. However, the effective utilization of the millimeter-wave (mmWave) as a critical enabler of foreseen potential in 6G, poses significant challenges due to its unique propagation characteristics and security concerns. Deep learning (DL)/machine learning (ML) based approaches emerged as potential solutions; however, DL/ML contains centralization and data privacy issues. Therefore, federated learning (FL), an innovative decentralized DL/ML paradigm, offers a promising avenue to tackle these challenges by enabling collaborative model training across distributed devices while preserving data privacy. After a comprehensive exploration of FL enabled 6G networks, this review identifies the specific applications of mmWave communications in the context of FL enabled 6G networks. Thereby, this article discusses particular challenges faced in the adaption of FL enabled mmWave communication in 6G; including bandwidth consumption, power consumption and synchronization requirements. In view of the identified challenges, this study proposed a way forward called Federated Energy-Aware Dynamic Synchronization with Bandwidth-Optimization (FEADSBO). Moreover, this review highlights pertinent open research issues by synthesizing current advancements and research efforts. Through this review, we provide a roadmap to harness the synergies between FL and mmWave, offering insights to reshape the landscape of 6G networks.
Genetic profile of the whole genome sequence of African swine fever virus from the first outbreak in Malaysian Borneo

Azami MM, Pauzi NAS, Hamdan N, Sidik MR, Tulis AN, Hassan R, et al.

Vet Res Commun, 2025 Jan 15;49(2):77.
PMID: 39809923 DOI: 10.1007/s11259-025-10645-8

African swine fever (ASF), a severe and highly contagious haemorrhagic viral disease of pigs, is becoming a major threat not only in Malaysia but around the world. The first confirmed case of ASF in Malaysia was reported in February 2021. Despite the emergence of ASF in Malaysia, genetic information on this causative pathogen for the local livestock is still limited. This study aimed to genetically characterize the African swine fever virus (ASFV) responsible for the 2021 outbreak in Malaysia. The genome of the ASFV isolated during the first outbreak in Malaysia was analysed as ASFV/Sabah/Malaysia/1160/21 which has 190,594 base pairs, with a nitrogenous bases (GC) content of 40.33% and 195 predicted Open Reading Frames (ORF). The complete genome sequence was compared with other annotated ASFV genomes retrieved from database of National Center for Biotechnology Information (NCBI) to obtain information based on target gene B646L, E183L, intergenic region (IGR) between I73R and I329L (IGRI73R-I329L), EP402R and B602L. The ASFV/Sabah/Malaysia/1160/21 genome had a high similarity percentage to the reference genome, Georgia 2007 and all Southeast Asian strains. Phylogenetic analysis revealed that the ASFV strain belonged to genotype II, serogroup 8, CVR1 and showed high characteristics of IGR variant II based on IGRI73R-I329L. This study expands our understanding of genetic diversity and provides significant insights into the genomic characteristics and variation of ASFV strains that are circulating in Malaysia.
Fulltext HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, et al.

Biomed Res Int, 2013;2013:129715.
PMID: 23484077 DOI: 10.1155/2013/129715

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673-12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.
Fulltext Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients

Elias MH, Baba AA, Husin A, Abdullah AD, Hassan R, Sim GA, et al.

Hematol Rep, 2012 Nov 19;4(4):e23.
PMID: 23355941 DOI: 10.4081/hr.2012.e23

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCR-ABL kinase domain mutations using dHPLC followed by sequencing, and also status of BCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5%). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCR-ABL independent pathways. Different mutations confer different levels of resistance and, therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.
Fulltext Guidelines for nucleic acid detection and analysis in hematological disorders

Hassan R, Husin A, Sulong S, Yusoff S, Johan MF, Yahaya BH, et al.

Malays J Pathol, 2015 Aug;37(2):165-73.
PMID: 26277676 MyJurnal

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