Displaying publications 301 - 320 of 465 in total

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  1. MyJurnal
    The present study was to evaluate the toxicity of damnacanthal, nordamnacanthal, betulinic acid and zerumbone isolated from local medicinal plants towards leukemia cell lines and immune cells by using MTT assay and flow cytometry cell cycle analysis. The results showed that damnacanthal significantly inhibited HL-60 cells, CEM-SS and WEHI-3B with the IC50 value of 4.0 µg/mL, 8.0 µg/mL and 3.3 µg/mL, respectively. Nordamnacanthal and betulinic acid showed stronger inhibition towards CEM-SS and HL-60 cells with the IC50 value of 5.7 µg/mL and 5.0 µg/mL, respectively. In contrast, Zerumbone was demonstrated to be more toxic towards those leukemia cells with the IC50 value less than 10 µg/mL. Damnacanthal, nordamnacanthal and betulinic acid were not toxic towards 3T3 and PBMC compared to doxorubicin which showed toxicity effects towards 3T3 and PBMC with the IC50 value of 3.0 µg/mL and 28.0 µg/mL, respectively. The cell cycle analysis exhibited that damnacanthal exerted its toxicity effect towards HL-60 cells by inducing apoptosis with value of 25% after 72 hours treatment. Thus, these compounds could be the potential anticancer drug with less toxic side effect.
    Matched MeSH terms: Leukemia
  2. Mohamed Yusoff AA, Zulfakhar FN, Sul’ain MD, Idris Z, Abdullah JM
    Asian Pac J Cancer Prev, 2016 12 01;17(12):5195-5201.
    PMID: 28125199
    Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  3. Chua LL, Rajasuriar R, Azanan MS, Abdullah NK, Tang MS, Lee SC, et al.
    Microbiome, 2017 03 20;5(1):35.
    PMID: 28320465 DOI: 10.1186/s40168-017-0250-1
    BACKGROUND: Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include chronic inflammation-related comorbidities such as obesity and type 2 diabetes, but the underlying cause is poorly understood.

    RESULTS: We compared the anal microbiota composition of adult survivors of childhood ALL (N = 73) with healthy control subjects (N = 61). We identified an altered community with reduced microbial diversity in cancer survivors, who also exhibit signs of immune dysregulation including increased T cell activation and chronic inflammation. The bacterial community among cancer survivors was enriched for Actinobacteria (e.g. genus Corynebacterium) and depleted of Faecalibacterium, correlating with plasma concentrations of IL-6 and CRP and HLA-DR+CD4+ and HLA-DR+CD8+ T cells, which are established markers of inflammation and immune activation.

    CONCLUSIONS: We demonstrated a relationship between microbial dysbiosis and immune dysregulation in adult ALL survivors. These observations suggest that interventions that could restore microbial diversity may ameliorate chronic inflammation and, consequently, development of late effects of childhood cancer survivors.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology*
  4. Siti Aishah Md Ali, Ilina Isahak, Dahlan Sabil, Fatimah Sahlan, Lokman Saim, Abdullah Sani Mohamed
    Medicine & Health, 2006;1(1):5-13.
    MyJurnal
     
    The reciprocal translocation t(9;22)(q34;q11) which gives rise to the Philadelphia (Ph1) chromosome and BCR/ABL fusion gene, plays a pivotal role in the diagnosis and pathogenesis of chronic myeloid leukemia (CML). In this study, we evaluated the role of fluorescence in situ hybridisation (FISH) in detecting the BCR/ABL rearrangement in CML patients. The sensitivity, specificity and detection rate of BCR/ABL gene using FISH, PCR and conventional cytogenetics (karyotyping) methods were also compared. 18 bone marrow samples of patients with clinically diagnosed CML and suspected of CML were collected. The sensitivity, specificity and positive predictive values of FISH were altogether 100% while the sensitivity, specificity and positive predictive values for conventional cytogenetics (karyotyping) were 85%, 100% and 100% respectively. Convetional cytogenetics (karyotyping) detected an additional chromosomal aberration in addition to the Ph1 chromosome. In conclusion, FISH is a highly sensitive method in detecting the BCR/ABL gene. Conventional cytogenetics (karyotyping) remains an important investigation in the work up of suspected CML patients since there is a possibility of detecting chromosomal aberrations in addition to the Ph1 translocation. Therefore, conventional cytogenetics (karyotyping) and FISH are complementary techniques and their results should be interpreted together with clinical information.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  5. Zahilah, Z., Fadzil, A., Jamal, R.
    MyJurnal
    Life (QOL) of patients with childhood leukaemias presenting at the Hospital Universiti Kebangsaan Malaysia (HUKM). The objectives of this pilot study were 1) To assess the feasibility and applicability of assessing quality of life in leukaemia patients using the adult-based SF-36 questionnaire. 2) To compare the differences of QOL scores among patients based on gender and treatment status. The Short-Form-36 Health Survey (SF36) was used. The items in SF-36 were drawn from the original 245-item MOS questionnaire, which includes multi-item scales that measured the eight dimensions of quality of life namely physical function, role limitations (physical problems), bodily pain, general health, vitality, social functioning, role limitations (emotional problems) and mental health. Patients with acute leukaemias were chosen to participate in the study. Twenty-eight patients were recruited, twelve were males and 16 were females. Ten patients had completed therapy whilst 18 others were still undergoing treatment. The results showed that those patients off treatment have a better quality of life than those on chemotherapy. However, this was only significant with respect to the role limitation pertaining to physical problems. Although the use of the SF-36 was feasible, there were limitations especially in the younger age group.
    Matched MeSH terms: Leukemia
  6. Kamarulzaman, F. A., Mohamad, K., Awang, K., Lee, H. B.
    MyJurnal
    Our continuing research on the Aglaia genus (family Meliaceace) has led us to this first study on the chemical constituents of Aglaia lanuginose (bark). The dichloromethane extract from the bark of Aglaia lanuginose showed cytotoxicity against HL-60 leukaemia cell line (45% inhibition) at 20 µg/ml and was prioritised for further investigation. Repeated chromatography of the dichloromethane extract yielded the known dammarane triterpenes which were identified as cabralealactone (1), methyl eichlerianate (2), cabraleone (3), ocotillone (4), eichleriatone (5), eichlerianic acid (6) and shoreic acid (7) together with the known sterols, sitosterol (9) and stigmasterol (10). Another isolated compound was the aromatic 4-hydroxycinnamyl-acetate (8), which has not been reported to be present in a plant from the Meliaceae family. The structures of all the compounds were elucidated on the basis of spectroscopic methods (IR, MS and NMR). Cytotoxicity testing of 1-10 showed activity only for mixtures of (3, 4), and (5, 6).
    Matched MeSH terms: Leukemia
  7. Norazah Z, Joyce Darshinee DS
    Med J Malaysia, 2018 04;73(2):119-120.
    PMID: 29703879 MyJurnal
    Pulmonary veins stenosis in a Down Syndrome infant with normal connection pulmonary vein is rare and precise incidence of this disease is unknown. We report a case of progressive multiple pulmonary vein stenosis in a Down Syndrome infant with congenital heart disease and transient myeloproliferative leukaemia. This case-report aims to improve awareness among physicians and sonographers of this disease and the importance of pulmonary vein assessment in congenital heart disease with unexplained pulmonary hypertension.
    Matched MeSH terms: Leukemia
  8. Tang YL, Chia WK, Yap EC, Julia MI, Leong CF, Salwati S, et al.
    Malays J Pathol, 2016 Dec;38(3):315-319.
    PMID: 28028303 MyJurnal
    INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival.

    CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.

    DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*; Leukemia, Promyelocytic, Acute/drug therapy*
  9. Lim YM, Eng WL, Chan HK
    Asian Pac J Cancer Prev, 2017 07 27;18(7):1925-1930.
    PMID: 28749622
    Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the
    Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to
    tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian
    CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted
    with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis
    approach. Results: The patients generally demonstrated inadequate knowledge, particularly of the natural history and
    staging of CML, the function of TKIs, and the methods used for monitoring the effectiveness of treatment. A number of
    them also had experiences of withholding, skipping or altering the treatment, mainly due to the life-disturbing adverse
    drug effects (ADRs), forgetfulness, and religious and social issues. Besides, most of them were found having limited
    skills in managing the ADRs, and not using prompts as reminders to take the medications. Furthermore, even though
    nilotinib was generally perceived as better tolerated as compared with imatinib, the inconvenience caused by the need
    to take it twice daily and on an empty stomach was constantly highlighted by the patients. Conclusion: While TKIs
    are widely used for CML treatment in Malaysia, the findings have revealed a lack of patient education and awareness,
    which warrants an integrated plan to reinforce medication adherence.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  10. Fahisham Taib, Lee, Chee Chan
    MyJurnal
    Palliative care for life limiting conditions usually starts at birth. In neonatal period, planning,
    discussion and goal of care should focus towards improving the baby quality of life. It does not mean
    palliative care in this age group mainly as end of life care. We illustrate a complex 30 weeks baby
    who was born with genetic abnormality complicated with intracranial bleeding and acute myeloid
    leukaemia. There were various ethical issues related to the approach of death and dying infant and
    psychosocial challenges surrounding the case.
    Matched MeSH terms: Leukemia
  11. M.R. Mohd Hafiz, M.Z. Mazatulikhma, F.A. Mohd Faiz, M.S. Mohamed Saifulaman
    Sains Malaysiana, 2013;42:1131-1137.
    In this study, RNA interference (RNAi) was carried out as an experimental technique to knockdown three mitogen-activated protein kinase (MAPK) pathway genes, raf-1, mekk1 and mlk3 in acute myeloid leukemia (AML) cells. Conventionally, RNAi knockdown experiments target a single gene for functional studies or therapeutic purposes. We wanted to explore the potential differences or similarities between targeting single targets or multiple target genes in a single application. We achieved knockdown of gene expression levels of between 40 and 60% for the RNAi experiments, with better knockdown observed in single target gene experiments in comparison with the multiple target gene experiment. Microarray analysis indicated that the transfection process had most likely induced the immune response from the cells in every RNAi treatment. This might indicate that when the MAPK signaling pathway is partially blocked, in tandem with the immune response, the cells will begin signaling for apoptosis leading to cellular death of the leukemic cells.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  12. Zhang Y, Lee S, Xu W
    Biochem Biophys Res Commun, 2020 04 16;524(4):1018-1024.
    PMID: 32063363 DOI: 10.1016/j.bbrc.2020.02.021
    Pten deletion in the hematopoietic stem cells (HSC) causes a myeloproliferative disorder, which may subsequently develop into a T-cell acute lymphoblastic leukemia (T-ALL). β-catenin expression was dramatically increased in the c-KitmidCD3+Lin- leukemia stem cells (LSC) and was critical for T-ALL development. Therefore, the inactivation of β-catenin in LSC may have a potential to eliminate the LSC. In this study, we investigated the mechanism of enhancement of the β-catenin expression and subsequently used a drug to inactivate β-catenin expression in T-ALL. Western blot (WB) analysis revealed an increased level of β-catenin in the leukemic cells, but not in the pre-leukemic cells. Furthermore, the WB analysis of the thymic cells from different stages of leukemia development showed that increased expression of β-catenin was not via the pS9-GSK3β signaling, but was dependent on the pT308-Akt activation. Miltefosine (Hexadecylphosphocholine) is the first oral anti-Leishmania drug, which is a phospholipid agent and has been shown to inhibit the PI3K/Akt activity. Treatment of the PtenΔ/Δ leukemic mice with Miltefosine for different durations demonstrated that the pT308-Akt and the β-catenin expressions were inhibited in the leukemia blast cells. Miltefosine treatment also suppressed the TGFβ1/Smad3 signaling pathway. Analysis of TGFβ1 in the sorted subpopulations of the blast cells showed that TGFβ1 was secreted by the CD3+CD4- subpopulation and may exert effects on the subpopulations of both CD3+CD4+ and CD3+CD4- leukemia blast cells. When a TGFβR1 inhibitor, SB431542 was injected into the PtenΔ/Δ leukemic mice, the Smad3 and β-catenin expressions were down-regulated. On the basis of the results, we conclude that Miltefosine can suppress leukemia by degrading β-catenin through repression of the pT308-Akt and TGFβ1/Smad3 signaling pathways. This study demonstrates a possibility to inhibit Pten loss-associated leukemia genesis via targeting Akt and Smad3.
    Matched MeSH terms: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism
  13. Gan GG, Ng DLC, Leong YC, Bee PC, Chin EFM, Abdul Halim H, et al.
    Med J Malaysia, 2019 Jun;74(3):191-197.
    PMID: 31256172
    BACKGROUND: It is not uncommon that anxiety and depression occur in patients with cancers, and past researches have shown that the quality of life of patients is negatively affected. This study aims to determine the prevalence of anxiety and depression of patients with haematological cancers in Malaysia and to investigate the possible association of these psychological symptoms with their quality of life.

    METHODS: This is a cross-sectional study where patients with haematological cancers attending two major hospitals were recruited. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression scale (HADS). Quality of life (QoL) of these patients was measured using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30). An overall summary QoL score in combination with financial difficulty score and global health score were used for analysis.

    RESULTS: A total of 319 patients were recruited. Thirty-three percent of patients had anxiety symptoms, 23.5% had depression symptoms. In summary the overall score of QoL is significantly lower in patients with higher scores for depression and anxiety, (p<0.05). Patients who exhibit anxiety symptoms were more frequently female, still undergoing treatment whereas patients who had higher depression scores were older and had acute leukemias or myeloproliferative neoplasms. Patients who have depression are significantly associated with a higher financial difficulty score, p<0.05.

    CONCLUSION: The poor quality of life in patients who have anxiety and depression should raise awareness amongst the health professions treating them so that additional support can be provided.

    Matched MeSH terms: Leukemia
  14. Oh L, Hainaut P, Blanchet S, Ariffin H
    BMC Cancer, 2020 Feb 10;20(1):110.
    PMID: 32041553 DOI: 10.1186/s12885-020-6599-8
    BACKGROUND: TP53 mutations occur in only about 3% of primary and 10-20% of relapse B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). However, alternative mechanisms may contribute to functionally impairing the p53 pathway in the absence of a mutation. Candidate mechanisms include overexpression of p53 mRNA variants encoding either dominant-negative p53 protein isoforms such as Delta40p53 and Delta133p53, or modulatory isoforms such as p53beta, which counteract the effects of Delta133p53 on replicative senescence in T-lymphocytes.

    METHODS: We used semi-quantitative reverse-transcriptase PCR (RT-PCR) and Western blot to investigate the expression of full length p53 (TAp53), Delta40p53, Delta133p53 or p53beta in diagnostic marrow from a clinical cohort of 50 BCP-ALL patients without TP53 mutation (29 males and 21 females, age range 2-14 years) and in the bone marrow cells of 4 healthy donors (used as controls).

    RESULTS: Irrespective of isoforms, levels of p53 mRNA were low in controls but were increased by 2 to 20-fold in primary or relapse BCP-ALL. TAp53 was increased in primary BCP-ALL, Delta40p53 was elevated in relapse BCP-ALL, whereas Delta133p53 and p53beta were increased in both. Next, mRNA levels were used as a basis to infer the ratio between protein isoform levels. This inference suggested that, in primary BCP-ALL, p53 was predominantly in active oligomeric conformations dominated by TAp53. In contrast, p53 mostly existed in inactive quaternary conformations containing ≥2 Delta40 or Delta133p53 in relapse BCP-ALL. Western blot analysis of blasts from BCP-ALL showed a complex pattern of N-terminally truncated p53 isoforms, whereas TAp53beta was detected as a major isoform. The hypothesis that p53 is in an active form in primary B-ALL was consistent with elevated level of p53 target genes CDKN1A and MDM2 in primary cases, whereas in relapse BCP-ALL, only CDKN1A was increased as compared to controls.

    CONCLUSION: Expression of p53 isoforms is deregulated in BCP-ALL in the absence of TP53 mutation, with increased expression of alternative isoforms in relapse BCP-ALL. Variations in isoform expression may contribute to functional deregulation of the p53 pathway in BCP-ALL, specifically contributing to its down-regulation in relapse forms.

    Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology*; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy
  15. Annuar AA, Ankathil R, Mohd Yunus N, Husin A, Ab Rajab NS, Abdul Aziz AA, et al.
    Asian Pac J Cancer Prev, 2021 Feb 01;22(2):565-571.
    PMID: 33639675 DOI: 10.31557/APJCP.2021.22.2.565
    BACKGROUND: The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.

    METHODS: This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.

    RESULTS: We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.

    CONCLUSION: The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.

    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
  16. Zakaria Z, Othman N, Ismail A, Kamaluddin NR, Esa E, Abdul Rahman EJ, et al.
    Asian Pac J Cancer Prev, 2017 04 01;18(4):1169-1175.
    PMID: 28548470
    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. Methods: DNA was isolated from bone marrow samples
    using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We
    identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533
    variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were
    deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956
    were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11
    nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related
    genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17,
    CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are
    important in identifying new therapeutic targets and developing rationally designed treatment regimens with less
    toxicity in ALL patients.
    Matched MeSH terms: Leukemia
  17. Chai KS, Norsarwany M, Shatriah I
    Cureus, 2017 Aug 16;9(8):e1573.
    PMID: 29057185 DOI: 10.7759/cureus.1573
    Ptosis is a rare side effect of vincristine chemotherapy in patients treated for cancer. We report a case of a child with common B-cell acute lymphoblastic leukemia who developed bilateral moderate ptosis following the chemotherapy protocol of the United Kingdom Acute Lymphoblastic Leukemia (ALL) regimen A. The patient showed dramatic clinical improvement after a combination of oral pyridoxine and thiamine treatment. We provide a literature review of this uncommon presentation.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  18. Islam M, Mohamed Z, Assenov Y
    Int J Genomics, 2017;2017:2913648.
    PMID: 28713819 DOI: 10.1155/2017/2913648
    Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  19. Ismail NZ, Mohamed WAS, Ab Rahim N, Hashim NM, Adebayo IA, Mohamad Zain NN, et al.
    J Biomol Struct Dyn, 2023;41(13):6104-6120.
    PMID: 35899385 DOI: 10.1080/07391102.2022.2101530
    Clinacanthus nutans is a medicinal plant recognised for its anticancer properties. We previously discovered that the C. nutans extract had the most potent inhibitory effect on MCF7 breast cancer cell and significantly induced apoptosis. However, there is a scarcity of studies demonstrating the molecular interactions of C. nutans-derived chemical compounds associated with apoptosis-related proteins. Therefore, the objective of this study was to determine the potential chemical compounds found in the C. nutans extract and examine their interactions with the targeted apoptotic proteins using molecular docking and molecular dynamic simulations. To address this objective, the compounds found in the SF2 extract of C. nutans were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). The molecular interaction of the compounds with the targeted apoptotic proteins were determined using molecular docking and molecular dynamic simulations. GC-MS analysis revealed a total of 32 compounds in the SF2 extract. Molecular docking analysis showed that compound β-amyrenol had the highest binding affinity for MDM2-P53 (-7.26 kcal/mol), BCL2 (-11.14 kcal/mol), MCL1-BAX (-6.42 kcal/mol), MCL1-BID (-6.91 kcal/mol), and caspase-9 (-12.54 kcal/mol), whereas campesterol had the highest binding affinity for caspase-8 (-10.11 kcal/mol) and caspase-3 (-10.14 kcal/mol). These selected compounds were subjected to molecular dynamic simulation at 310 K for 100 ns. The results showed that the selected protein-ligand conformation complexes were stable, compact, and did not alter much when compared to the protein references. The findings indicate that β-amyrenol and campesterol are potentially significant compounds that might provide insight into the molecular interactions of the compounds with the apoptosis-related proteins.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Myeloid Cell Leukemia Sequence 1 Protein
  20. Krishnan GD, Zakaria MH, Yahaya N
    J ASEAN Fed Endocr Soc, 2020;35(2):163-168.
    PMID: 33442187 DOI: 10.15605/jafes.035.02.03
    Introduction: Vitamin B12 deficiency is more common among metformin-treated subjects although the prevalence is variable. Many factors have been associated with this. The aim of this study is to determine the prevalence of vitamin B12 deficiency and its associated factors among patients with type 2 diabetes mellitus (DM) who are on metformin.

    Methodology: A total of 205 patients who fit eligibility criteria were included in the study. A questionnaire was completed, and blood was drawn to study vitamin B12 levels. Vitamin B12 deficiency was defined as serum B12 level of ≤300 pg/mL (221 pmol/L).

    Results: The prevalence of vitamin B12 deficiency among metformin-treated patients with type 2 DM patients was 28.3% (n=58). The median vitamin B12 level was 419 (±257) pg/mL. The non-Malay population was at a higher risk for metformin-associated vitamin B12 deficiency [adjusted odds ratio (OR) 3.86, 95% CI: 1.836 to 8.104, p<0.001]. Duration of metformin use of more than five years showed increased risk for metformin-associated vitamin B12 deficiency (adjusted OR 2.06, 95% CI: 1.003 to 4.227, p=0.049).

    Conclusion: Our study suggests that the prevalence of vitamin B12 deficiency among patients with type 2 diabetes mellitus on metformin in our population is substantial. This is more frequent among the non-Malay population and those who have been on metformin for more than five years.

    Matched MeSH terms: Leukemia, Myeloid, Acute
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