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Fulltext Aberrant Methylation of Tumour Suppressor Gene ADAM12 in Chronic Lympocytic Leukemia Patients: Application of Methylation Specific-PCR Technique

Mohamad A, Hassan R, Husin A, Johan MF, Sulong S

Asian Pac J Cancer Prev, 2021 Jan 01;22(1):85-91.
PMID: 33507683 DOI: 10.31557/APJCP.2021.22.1.85

OBJECTIVE: Chronic Lymphocytic Leukemia (CLL) is a common leukemia among Caucasians but rare in Asians population. We postulated that aberrant methylation either hypermethylation or partial methylation might be one of the silencing mechanisms that inactivates the tumour suppressor genes in CLL. This study aimed to compare the methylation status of tumour suppressor gene, ADAM12, among CLL patients and normal individuals. We also evaluated the association between methylation of ADAM12 and clinical and demographic characteristics of the participants.
METHODS: A total of 25 CLL patients and 25 normal individuals were recruited in this study. The methylation status of ADAM12 was determined using Methylation-Specific PCR (MSP); whereas, DNA sequencing method was applied for validation of the MSP results.
RESULTS: Among CLL patients, 12 (48%) were partially methylated and 13 (52%) were unmethylated. Meanwhile, 5 (20%) and 20 (80.6%) of healthy individuals were partially methylated and unmethylated, respectively. There was a statistically significant association between the status of methylation at ADAM12 and the presence of CLL (p=0.037).
CONCLUSION: The aberrant methylation of ADAM12 found in this study using MSP assay may provide new exposure to CLL that may improve the gaps involved in genetic epigenetic study in CLL.
An Epidemiology Study of Adult Immune Thrombocytopenia Patients in a Teaching Hospital in Northeastern Malaysia

Zahidin MA, Abdul Razak NI, Mohd Noor NH, Johan MF, Zulkafli Z, Abdullah AD, et al.

Cureus, 2023 Nov;15(11):e48533.
PMID: 38073971 DOI: 10.7759/cureus.48533

Immune thrombocytopenia (ITP) has been comprehensively studied and understood in Western Europe and various Asia-Pacific regions. However, the epidemiological and clinical-laboratory aspects of ITP in Malaysia remain limited and not well documented. Therefore, this study aims to evaluate the incidence and clinical parameters of ITP using 20-year retrospective data. Medical records for 205 consecutive adult patients with ITP between January 2000 and December 2022 were analyzed. A p-value of <0.05 is considered statistically significant. The majority were Malays (n=192, 93.7%) and females (n=150, 73.2%), with a male-to-female ratio of 1:2.73. One hundred thirty-two (64.4%) and 73 (35.6%) patients were diagnosed with primary ITP (pITP) and secondary ITP (sITP), respectively. Systemic lupus erythematosus (SLE) (n=23, 35.9%), antiphospholipid syndrome (APS) (n=5, 7.8%), and familial thrombocytopenia (n=5, 7.8%) were the top 3 comorbid conditions for ITP. The overall incidence was 1.80/100,000 person-years (95% confidence interval (CI): 1.56-2.07), and the incidences were higher in females than in males with pITP (1.78/100,000 person-years versus 0.70/100,000 person-years) and sITP (0.86/100,000 person-years versus 0.26/100,000 person-years). The median age for patients with pITP was significantly higher than for those with sITP (median: 44 versus 37 years, respectively) (p=0.026). However, there was no statistically significant difference in white blood cell (WBC) counts, hemoglobin (HB) counts, platelet (PLT) counts, absolute neutrophil counts (ANC), or hematocrit (HCT) counts between those with pITP and sITP at the time of diagnosis. The current study provides an overview of ITP epidemiology in northeastern Malaysia. We emphasize the critical need for further additional research, particularly at the state and national levels in the future.
Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

Zamani A, Mat Jusoh SA, Al-Jamal HA, Sul'ain MD, Johan MF

Asian Pac J Cancer Prev, 2016 11 01;17(11):4857-4861.
PMID: 28030911

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
Anti-Proliferative Effects of Methanol and Water Extracts of Pyrrosia piloselloides on the Hela Human Cervical Carcinoma Cell Line

Sul ‘ain MD, Zakaria F, Johan MF

Asian Pac J Cancer Prev, 2019 Jan 25;20(1):185-192.
PMID: 30678430

Background: Cervical cancer is one of the most commonly diagnosed neoplasms and a leading cause of cancer
death among females worldwide. Limitations with conventional medical treatments have driven researchers to
search for alternative approaches using natural products. This study aimed to detemine potential anti-proliferative
effects of methanol and water extracts of Pyrrosia piloselloides (P. piloselloides) on the HeLa cell line. Methods:
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine IC50
concentrations and apoptosis analysis was by flow cytometry. To identify chemical compounds in the extracts, gas
chromatography-mass spectrometry (GC-MS) was employed. Results: P. piloselloides methanol extracts (PPME) showed
antiproliferative effects on HeL awith an IC50 of 16.25μg/mL while the P. piloselloides water extract (PPWE) was without
influence. Neither extract showed any significant effects on apoptosis. GC-MS analysis, revealed 5-hydroxymethylfurfural
(23.1%), allopurinol (8.66%) and 3, 5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (7.41%) as major components in
the PPME, while sulfolan-3-ol (10.1%), linoleic acid (9.06%) and β-sitosterol acetate (7.98%) predominated in the
PPWE case. Conclusion: This first study of P. piloselloides showed PPME to exert potent anti-proliferative effect on
HeLa cell lines. Further research now needs to be performed to establish the mechanisms of inhibition.
Fulltext Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study

Khan AYF, Ahmed QU, Narayanamurthy V, Razali S, Asuhaimi FA, Saleh MSM, et al.

Biomed Pharmacother, 2019 Jun;114:108841.
PMID: 30981106 DOI: 10.1016/j.biopha.2019.108841

Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
Apoptosis induction in MV4-11 and K562 human leukemic cells by Pereskia sacharosa (Cactaceae) leaf crude extract

Asmaa MJ, Al-Jamal HA, Ang CY, Asan JM, Seeni A, Johan MF

Asian Pac J Cancer Prev, 2014;15(1):475-81.
PMID: 24528077

BACKGROUND: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia.
MATERIALS AND METHODS: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting.
RESULTS: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells.
CONCLUSIONS: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.
Fulltext Apoptotic induction in cCCRF-CEM and HL human leukemic cell lines by 5-azacitidine and trichostatin A

Aziee, S., Haiyuni, MY, Shafini, MY, Johan, MF, Al-Jamal, HAN, Abdul Wahab, R., et al.

Journal of Biomedical and Clinical Sciences, 2018;3(1):54-61.
MyJurnal

The aims of the study were to investigate the anti-cancer effects of 5-
Aza and TSA in two leukemic cell lines (CCRF-CEM and HL-60). Inhibition
concentration of 5-Aza and TSA were measured using trypan blue exclusion
assay. 5-Aza and TSA at IC50 were treated to both CCRF-CEM and HL-60 cell
lines for 4-6 days. To confirm the inhibition effects of these agents, Annexin-V
stained cells were analyzed using flow cytometry to evaluate the apoptotic
induction. The IC50 values of CCRF-CEM were 2.01±0.1µM and 2.65±0.3µM for
5-Aza- and TSA-treated, respectively. Whereas, the IC50 values of HL-60 were
1.98±0.2µM and 2.35±0.2µM for 5-Aza- and TSA-treated, respectively. To
further substantiate the findings, the time-dependent exposure of both drugs was
studied. CCRF-CEM cells were reduced to 49.4%±5.0, 49.4%±2.5 and
41.5%±5.6 by 5-Aza; 56.5%±7.0, 45.3%±4.2 and 40.2%±4.2 by TSA treatment
at first, third and sixth day. HL-60 cells were reduced to 72.0%±4.5, 51.0%±1.5
and 40.6%±2.6 by 5-Aza at first, third and sixth day. Meanwhile, HL-60 cells
reduced to 55.6%±4.5, 45.2%±4.0 and 36.3%±2.9 by TSA at first, second and
fourth day. Both cell lines were significantly inhibited (p
Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Yunus NM, Johan MF, Ali Nagi Al-Jamal H, Husin A, Hussein AR, Hassan R

Asian Pac J Cancer Prev, 2015;16(12):4869-72.
PMID: 26163606

BACKGROUND: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis.
MATERIALS AND METHODS: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia.
RESULTS: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374).
CONCLUSIONS: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.
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.
Conformation sensitive gel electrophoresis for the detection of calreticulin mutations in BCR-ABL1-negative myeloproliferative neoplasms

Zakaria NA, Rosle NA, Siti Asmaa MJ, Aziee S, Haiyuni MY, Samat NA, et al.

Int J Lab Hematol, 2021 Dec;43(6):1451-1457.
PMID: 34125992 DOI: 10.1111/ijlh.13628

INTRODUCTION: Calreticulin (CALR) mutations in myeloproliferative neoplasms (MPN) have been reported to be key markers in the molecular diagnosis, particularly in patients lacking JAK2 V617F mutation. In most current reports, CALR mutations were analysed by either allele-specific PCR (AS-PCR), or the more expensive quantitative real-time PCR, pyrosequencing and next-generation sequencing. Hence, we report the use of an alternative method, the conformation sensitive gel electrophoresis (CSGE) for the detection of CALR mutations in BCR-ABL1-negative MPN patients.
METHODS: Forty BCR-ABL1-negative MPN patients' DNA: 19 polycythemia vera (PV), 7 essential thrombocytosis (ET) and 14 primary myelofibrosis (PMF), were screened for CALR mutations by CSGE. PCR primers were designed to amplify sequences spanning between exons 8 and 9 to target the mutation hotspots in CALR. Amplicons displaying abnormal CSGE profiles by electrophoresis were directly sequenced, and results were analysed by BioEdit Sequence Alignment Editor v7.2.6. CSGE results were compared with AS-PCR and confirmed by Sanger sequencing.
RESULTS: CSGE identified 4 types of mutations; 2 PMF patients with either CALR type 1 (c.1099_1150del52) or type 2 (c.1155_1156insTTGTC), 1 ET patient with nucleotide deletion (c.1121delA) and insertion (c.1190insA) and 1 PV patient with p.K368del (c.1102_1104delAAG) and insertion (c.1135insA) inframe mutations. Three patients have an altered KDEL motif at the C-terminal of CALR protein. In comparison, AS-PCR only able to detect two PMF patients with mutations, either type 1 and type 2.
CONCLUSION: CSGE is inexpensive, sensitive and reliable alternative method for the detection of CALR mutations in BCR-ABL1-negative MPN patients.
Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin

Ismail S, Haris K, Abdul Ghani AR, Abdullah JM, Johan MF, Mohamed Yusoff AA

J Asian Nat Prod Res, 2013 Sep;15(9):1003-12.
PMID: 23869465 DOI: 10.1080/10286020.2013.818982

Aloe emodin, one of the active compounds found in Aloe vera leaves, plays an important role in the regulation of cell growth and death. It has been reported to promote the anti-cancer effects in various cancer cells by inducing apoptosis. However, the mechanism of inducing apoptosis by this agent is poorly understood in glioma cells. This research is to investigate the apoptosis and cell cycle arrest inducing by aloe emodin on U87 human malignant glioma cells. Aloe emodin showed a time- and dose-dependent inhibition of U87 cells proliferation and decreased the percentage of viable U87 cells via the induction of apoptosis. Characteristic morphological changes, such as the formation of apoptotic bodies, were observed with confocal microscope by Annexin V-FITC/PI staining, supporting our viability study and flow cytometry analysis results. Our data also demonstrated that aloe emodin arrested the cell cycle in the S phase and promoted the loss of mitochondrial membrane potential in U87 cells that indicated the early event of the mitochondria-induced apoptotic pathway.
Fulltext Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia

Al-Jamal HA, Mat Jusoh SA, Hassan R, Johan MF

BMC Cancer, 2015;15:869.
PMID: 26547689 DOI: 10.1186/s12885-015-1695-x

Tumor-suppressor genes are inactivated by methylation in several cancers including acute myeloid leukemia (AML). Src homology-2 (SH2)-containing protein-tyrosine phosphatase 1 (SHP-1) is a negative regulator of the JAK/STAT pathway. Transcriptional silencing of SHP-1 plays a critical role in the development and progression of cancers through STAT3 activation. 5-Azacytidine (5-Aza) is a DNA methyltransferase inhibitor that causes DNA demethylation resulting in re-expression of silenced SHP-1. Lestaurtinib (CEP-701) is a multi-targeted tyrosine kinase inhibitor that potently inhibits FLT3 tyrosine kinase and induces hematological remission in AML patients harboring the internal tandem duplication of the FLT3 gene (FLT3-ITD). However, the majority of patients in clinical trials developed resistance to CEP-701. Therefore, the aim of this study, was to assess the effect of re-expression of SHP-1 on sensitivity to CEP-701 in resistant AML cells.
Evaluation of serological transfusion-transmitted viral diseases and mutliplex nucleic acid testing in malaysian blood donors

Yaseen SG, Ahmed SA, Johan MF, Kiron R, Daher AM

Transfus Apher Sci, 2013 Dec;49(3):647-51.
PMID: 23890575 DOI: 10.1016/j.transci.2013.07.003

Transmission of infectious diseases is a recognized complication of blood transfusion and blood products. Nucleic acid testing (NAT) may contribute to improved efficiency of blood screening and thereby increase the safety margin for transfused blood.
Genetic polymorphisms of HbE/beta thalassemia related to clinical presentation: implications for clinical diversity

Azman NF, Abdullah WZ, Hanafi S, Diana R, Bahar R, Johan MF, et al.

Ann Hematol, 2020 Apr;99(4):729-735.
PMID: 32078010 DOI: 10.1007/s00277-020-03927-5

HbE/Beta thalassemia (HbE/β-thalassemia) is one of the common genetic disorders in South East Asia. It is heterogeneous in its clinical presentation and molecular defects. There are genetic modifiers which have been reported to influence the disease severity of this disorder. The aim of this study was to determine the genetic polymorphisms which were responsible for the disease clinical diversity. A case-control study was conducted among Malay transfusion-dependent HbE/β-thalassemia patients. Patients who were confirmed HbE/β-thalassemia were recruited and genotyping study was performed on these subjects. Ninety-eight patients were selected and divided into moderate and severe groups based on clinical parameters using Sripichai scoring system (based on hemoglobin level, spleen size, growth development, the age of first transfusion and age of disease presentation). Forty-three (44.9%) and 55 (56.1%) patients were found to have moderate and severe clinical presentation, respectively. Genotyping analysis was performed using Affymetrix 6.0 microarray platform. The SNPs were filtered using PLINK and Manhattan plot by R software. From the GWAS results, 20 most significant SNPs were selected based on disease severity when compared between moderate and severe groups. The significant SNPs found in this study were mostly related to thalassemia complications such as rs7372408, associated with KCNMB2-AS1 and SNPs associated with disease severity. These findings could be used as genetic predictors in managing patients with HbE/β-thalassemia and served as platform for future study.
Fulltext Genotype-phenotype association of Hbe/β thalassemia disease and the role of genetic modifiers

HanafI S, Abdullah WZ, Adnan RA, Bahar R, Johan MF, Azman NF, et al.

Malaysian Journal of Paediatrics and Child Health, 2016;22(1):1-16.
MyJurnal

HbE/β-thalassemia is the most common severe form of thalassemia particularly in SEA region including Malaysia and globally, it comprised of a significant severe form of β-thalassemia disorder. It has various clinical manifestations ranging from very mild anemia to severe manifestation similar to beta thalassemia major. Many different syndromes are observed in HbE/β-thalassemia. Several genetic modifiers have been reported to play important role in contributing to phenotypic variability. The true reasons underlying this phenotypic variability remain unknown. The most reliable predictive factor of the disease phenotype is the nature of the beta globin gene mutation itself. However, the degree of severity is also believed to be affected by other genetic modifiers. For instance, high HbF level ameliorates the clinical severity of β thalassemia patients. Therefore, identification of these genetic modifiers is very important. The association of severe clinical manifestation and the specific β-globin gene mutation has been known. But the wide scope and other potential predictors have been only recently appreciated. This review therefore aimed to reveal the potential genetic modifiers of HbE/βthalassemia patients based on the previous reported studies. A better understanding on the mechanisms underlying the variety of phenotypes of this disease may lead to the direction for a better future management plans. This also promotes “personalized medicine” in patient care.
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
Identification and Quantification of Quercetin, A Major Constituent of Artocarpus altilis by Targeting Related Genes of Apoptosis and Cell Cycle: In Vitro Cytotoxic Activity Against Human Lung Carcinoma Cell Lines

Jalal TK, Khan AYF, Natto HA, Abdull Rasad MSB, Arifin Kaderi M, Mohammad M, et al.

Nutr Cancer, 2019;71(5):792-805.
PMID: 30614285 DOI: 10.1080/01635581.2018.1516790

Nine phenolic compounds were identified and quantified in Artocarpus altilia fruit. One of the main compounds was quercetin, which is the major class of flavonoids has been identified and quantified in pulp part of A. altilis fruit of methanol extract. The aim of this study was to evaluate in vitro cytotoxic assay. Inhibitory concentration 50% concentration was determined using trypan blue exclusion assay. Apoptosis induction and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell cycle-related regulatory genes were assessed by RT-qPCR study of the methanol extract of pulp part on human lung carcinoma (A549) cell line. A significant increase of cells at G2/M phases was detected (P
Mannose-binding lectin gene sequence data in Kelantan population

Zahidin MA, Mohd Noor NH, Johan MF, Abdullah AD, Zulkafli Z, Edinur HA

Sci Data, 2024 Apr 30;11(1):435.
PMID: 38688916 DOI: 10.1038/s41597-024-03274-4

The human mannose-binding lectin (MBL) gene encodes a polymorphic protein that plays a crucial role in the innate immune response. Human MBL deficiency is associated with immunodeficiencies, and its variants have been linked to autoimmune and infectious diseases. Despite this significance, gene studies concerning MBL sequencing are uncommon in Malaysia. Therefore, we aimed to preliminary described the human MBL sequencing dataset based on the Kelantan population. Blood samples were collected from 30 unrelated individuals and underwent DNA extraction, genotyping, and sequencing. The sequencing data generated 886 bp, which were deposited in GenBank (ON619541-ON619546). Allelic variants were identified and translated into six MBL haplotypes: HYPA, HYPB, LYPB, LXPB, HXPA, and LXPA. An evolutionary tree was constructed using the haplotype sequences. These findings contribute to the expansion of MBL information within the country, providing a valuable baseline for future research exploring the association between the gene and targeted diseases.
Fulltext Multiplex amplification refractory mutation system (MARMS) for the detection of β-globin gene mutations among the transfusion-dependent β-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia

Hanafi S, Hassan R, Bahar R, Abdullah WZ, Johan MF, Rashid ND, et al.

Am J Blood Res, 2014;4(1):33-40.
PMID: 25232503

The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.
Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells

Al-Jamal HAN, Johan MF, Mat Jusoh SA, Ismail I, Wan Taib WR

Asian Pac J Cancer Prev, 2018 Jun 25;19(6):1585-1590.
PMID: 29936783

Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and
progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways.
Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of
PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/
ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated
with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were
treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively.
Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation
status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in
K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased
in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed
higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to
imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling.

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