Displaying publications 61 - 80 of 464 in total

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  1. Fulltext Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer
    Fakiruddin KS, Lim MN, Nordin N, Rosli R, Zakaria Z, Abdullah S
    Cancers (Basel), 2019 08 28;11(9).
    PMID: 31466290 DOI: 10.3390/cancers11091261
    Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.
    Matched MeSH terms: Myeloid Cell Leukemia Sequence 1 Protein
  2. Targeted RNAi of the mitogen-activated protein kinase pathway genes in acute myeloid leukemia cells
    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
  3. TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population
    Mohammed Basabaeen AA, Abdelgader EA, Babekir EA, Abdelrahim SO, Eltayeb NH, Altayeb OA, et al.
    Asian Pac J Cancer Prev, 2019 May 25;20(5):1579-1585.
    PMID: 31128065
    Objective: This study aimed at exploring the association of TP53 72Arg/Pro polymorphism and Risk of Chronic
    Lymphocytic Leukemia and to assess the correlation between TP53 72Arg/Pro polymorphism and clinical parameter,
    hematological profile and some biological prognostic markers among Sudanese patients with chronic lymphocytic
    leukemia. Methods: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to
    April 2018, involved 110 B-CLL patients and 80 healthy volunteers as a control group. Physical examination, Complete
    Blood Count and Immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as
    Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from
    all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit (Germany) and analyzed
    TP53 codon 72Arg/Pro Polymorphism by using AS-PCR. The statistical analysis was performed using SPSS version
    23.0 software (Chicago, IL, USA). Results: the Arg/Pro was the most frequent genotype in B-CLL patients(50%),
    followed by Arg/Arg (25.5%) and Pro/Pro (24.5%), whereas in healthy control group Arg/Pro was the most frequent
    (47.5%), followed by Arg/Arg (45%) and Pro/Pro (7.5%). Our data indicate a higher frequency of homozygous Pro/
    Pro in the B-CLL patients as compared to controls with an OR of 4.01 for the Pro/Pro genotype and lower frequency
    of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype. Also, the
    Pro allele showed higher risk than Arg allele (P value=0.000, OR 2.23, 95% CI=1.45-3.41). No significant association
    between gender, clinical staging systems (Rai, Binet), biological prognostic markers (CD38 expression or ZAP70
    expression), and TP53 codon 72Arg/Pro polymorphisms, except Arg/Arg genotype tended to be associated with younger
    age (P =0.04). Conclusion: Our data suggested that Pro/Pro genotype contribute to increased susceptibility to B-Chronic
    Lymphocytic Leukemia risk in our population tenfold higher than those had Arg/Arg genotype.
    Matched MeSH terms: Leukemia, Lymphocytic, Chronic, B-Cell/genetics*
  4. TEL-AML1 frequency in multi-ethnic Malaysian pediatric acute lymphoblastic leukemia
    Gill HK, Keoh TS, Dhaliwal JS, Moore S, Kim TS, Hassan R, et al.
    Cancer Genet. Cytogenet., 2005 Jan 15;156(2):129-33.
    PMID: 15642392
    Eighty-eight multi-ethnic Malaysian pediatric acute lymphoblastic leukemia (ALL) patients were screened for the TEL-AML1 rearrangement by reverse transcription-polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was used as an independent screen for 30 cases and to confirm RT-PCR positive cases. Seventeen patients, or 19%, were found to be t(12;21) positive. Ethnically the group comprised 12 Malays, 4 Chinese, and 1 Indian. All patients, including 1 with an unusual blast cell morphology who suffered an early relapse and death, were characteristic TEL-AML1 cases in cell count, age, ALL subset classification, and fusion transcript expressed. This study shows that in Malaysia, TEL-AML1 is found in the same distinct ALL subset and at a similar frequency as in other diverse childhood ALL cohorts.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
  5. Systemic fusarium infection in cancer patients : a report of two cases
    Mohamed, M., Ariffin, H., Arasu, A., Tuck Soon, S.H., Abdullah, W.A., Lin, H.P.
    Malaysian Journal of Paediatrics and Child Health, 1998;10(2):55-58.
    MyJurnal
    Fusarium species is an emerging genus of fungal pathogens which until recently were rare causes of human disease apart from localized infection of the skin and nails. Two cases of fungaemia due to Fusarium sp. in children are described. The first child, an 8-year old girl with acute myeloid leukaemia developed character-sitic pyoderma gangrenosum-like skin lesions before succumbing to disseminated Fusarium infection and acute respiratory distress syndrome. The second child, a 5-month old boy, developed pneumonia associated with a transient erythematous skin rash while on chemother-apy for congenital leukaemia. Both patients had Fusarium isolated from blood. The second child improved after six weeks of treatment with ampho-tericin B and granulocyte-macrophage colony stimulat-ing factor but ultimately she died of the disease follow-ing discharge. Fusarium spp should be recognised as an opportunistic pathogen in immunocompromised patients. Current literature suggests that liposomal amphotericin B in conjunction with leukocyte growth factors are the treatment of choice in this potentially fatal infection.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  6. Systematic review of pre-clinical chronic myeloid leukaemia
    Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Int J Hematol, 2018 Nov;108(5):465-484.
    PMID: 30218276 DOI: 10.1007/s12185-018-2528-x
    BACKGROUND: Studies of a provisional entity pre-clinical chronic myeloid leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or blood/marrow feature of CML CP, has been increasing.

    OBJECTIVE: To perform a systematic review of pre-clinical CML and analysis the data relevant to disease progression to CML CP.

    METHOD: We performed a literature search on 16 July 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data and evaluated the quality of studies using an 8-item tool, independently. The outcomes were percentage of Philadelphia chromosome in the number of metaphases examined (Ph%), correlation between Ph% and blood count and time progress to CML.

    RESULT: Our initial search returned 4770 studies. A total of 10 studies with a total 17 subjects were included. The lowest Ph%, which eventually progresses to CML, was 10%. Absolute basophil count seemed to correlate better with Ph% compared to total white cell and absolute eosinophil count. The time from the first documented pre-clinical CML to CML ranged from 12 to 48 months. The overall quality of the included studies was average.

    CONCLUSION: This is the first systematic review on pre-clinical CML. This entity requires additional large-scale studies.

    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy; Leukemia, Myeloid, Chronic-Phase
  7. Systematic Review of an Automated Multiclass Detection and Classification System for Acute Leukaemia in Terms of Evaluation and Benchmarking, Open Challenges, Issues and Methodological Aspects
    Alsalem MA, Zaidan AA, Zaidan BB, Hashim M, Albahri OS, Albahri AS, et al.
    J Med Syst, 2018 Sep 19;42(11):204.
    PMID: 30232632 DOI: 10.1007/s10916-018-1064-9
    This study aims to systematically review prior research on the evaluation and benchmarking of automated acute leukaemia classification tasks. The review depends on three reliable search engines: ScienceDirect, Web of Science and IEEE Xplore. A research taxonomy developed for the review considers a wide perspective for automated detection and classification of acute leukaemia research and reflects the usage trends in the evaluation criteria in this field. The developed taxonomy consists of three main research directions in this domain. The taxonomy involves two phases. The first phase includes all three research directions. The second one demonstrates all the criteria used for evaluating acute leukaemia classification. The final set of studies includes 83 investigations, most of which focused on enhancing the accuracy and performance of detection and classification through proposed methods or systems. Few efforts were made to undertake the evaluation issues. According to the final set of articles, three groups of articles represented the main research directions in this domain: 56 articles highlighted the proposed methods, 22 articles involved proposals for system development and 5 papers centred on evaluation and comparison. The other taxonomy side included 16 main and sub-evaluation and benchmarking criteria. This review highlights three serious issues in the evaluation and benchmarking of multiclass classification of acute leukaemia, namely, conflicting criteria, evaluation criteria and criteria importance. It also determines the weakness of benchmarking tools. To solve these issues, multicriteria decision-making (MCDM) analysis techniques were proposed as effective recommended solutions in the methodological aspect. This methodological aspect involves a proposed decision support system based on MCDM for evaluation and benchmarking to select suitable multiclass classification models for acute leukaemia. The said support system is examined and has three sequential phases. Phase One presents the identification procedure and process for establishing a decision matrix based on a crossover of evaluation criteria and acute leukaemia multiclass classification models. Phase Two describes the decision matrix development for the selection of acute leukaemia classification models based on the integrated Best and worst method (BWM) and VIKOR. Phase Three entails the validation of the proposed system.
    Matched MeSH terms: Leukemia/diagnosis*
  8. Systematic Review of Normal Subjects Harbouring BCR-ABL1 Fusion Gene
    Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Acta Haematol., 2020;143(2):96-111.
    PMID: 31401626 DOI: 10.1159/000501146
    The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology*
  9. Fulltext Synergistic anti-proliferative effects of combination of ABT-263 and MCL-1 selective inhibitor A-1210477 on cervical cancer cell lines
    Lian BSX, Yek AEH, Shuvas H, Abdul Rahman SF, Muniandy K, Mohana-Kumaran N
    BMC Res Notes, 2018 Mar 27;11(1):197.
    PMID: 29580266 DOI: 10.1186/s13104-018-3302-0
    OBJECTIVE: There are number of studies which report that BCL-2 anti-apoptotic proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer tissues compared to the normal cervical epithelia. Despite these reports, targeting these proteins for cervical cancer treatment has not been explored extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may hold encouraging treatment outcomes for cervical cancer management. Hence, the aim of this pilot study is to investigate the sensitivity of cervical cancer cell lines to combination of two BH3-mimetics namely ABT-263 which selectively inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor.

    RESULTS: We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studies and drug sensitivity studies in physiological models are necessary to unleash the prospect of this combination for cervical cancer therapy.

    Matched MeSH terms: Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors*; Myeloid Cell Leukemia Sequence 1 Protein/metabolism
  10. Fulltext Sweet-like syndrome in a patient with acute myeloid leukaemia
    Norhaya MR, Cheong SK, Hamidah NH, Ainoon O
    Singapore Med J, 1996 Jun;37(3):320-2.
    PMID: 8942241
    A 45-year-old Malay lady developed brisk vesicular, plaque-like reaction to a Mantoux test concomitant with a diagnosis of acute myeloid leukaemia (AML). The lesion resolved one month after chemotherapy. Similar lesions developed later after she was bitten by mosquitoes on the forearms. She also had the lesions over her cheek. A skin biopsy showed infiltration of the dermis with neutrophils and some monocytoid cells. The lesion resolved one week after prednisolone therapy.
    Matched MeSH terms: Leukemia, Myeloid, Acute/complications; Leukemia, Myeloid, Acute/diagnosis*
  11. Fulltext Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome
    Raghuram N, Hasegawa D, Nakashima K, Rahman S, Antoniou E, Skajaa T, et al.
    Blood Adv, 2023 Nov 14;7(21):6532-6539.
    PMID: 36735769 DOI: 10.1182/bloodadvances.2022009381
    Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.
    Matched MeSH terms: Leukemia, Myeloid, Acute*
  12. Fulltext Survival of Children with Acute Leukaemia: A Single Centre Experience
    Ariffin Nasir, Nor Fadhilah Zahari, Fahisham Taib, Norsarwany Mohamad
    Malaysian Journal of Paediatrics and Child Health, 2020;26(1):4-13.
    MyJurnal
    Introduction: Acute leukaemia in children accounts for 25-30% of malignant diagnosis. Survival from acute leukaemia continue to improve. Treatment outcome depends on factors like gender, age at diagnosis, parental education, the initial total white cell count (TWC), cerebrospinal fluids (CSF) infiltration, immunophenotype and treatment response. Objectives: The objectives were to evaluate the survival of children with acute leukaemia who received chemotherapy and identify relevant factors. Methodology: The study was a retrospective record review at the Paediatric Oncology Unit, Hospital Universiti Sains Malaysia (Hospital USM). The data collected depending on pre-set research proforma from the year 1990 to 2010. Survival analysis of each type of leukaemia was completed using multiple Cox regression model. Results: A total of 334 cases were identified, only 283 patients received treatment at Hospital USM. There were 224 patients with acute lymphoblastic leukaemia (ALL) and 59 with acute myeloid leukaemia (AML). Overall survival (OS) rate at 3 months for ALL and AML were 89.3% and 72.9% respectively. The event-free survival (EFS) rate for ALL at 1, 3, and 5 years were 69.6%, 54.1% and 47.8% respectively. For AML, the EFS rate at 1, 3, and 5 years were 52.0%, 42.4% and 38.1% respectively. Multiple Cox regression model showed children’s age at diagnosis and early response to steroid therapy were the most significant prognostic factors for ALL survival, whereas the spleen size and treatment protocol were the most significant prognostic factors for AML. Conclusion: Survival rate in this study was comparable to developing countries. ALL had better outcome compared to AML.
    Matched MeSH terms: Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
  13. Survival and prognostic factors in Malaysian acute myeloid leukemia patients after allogeneic haematopoietic stem cell transplantation
    Mangantig E, Naing NN, Norsa'adah B, Azlan H
    Int J Hematol, 2013 Aug;98(2):197-205.
    PMID: 23719676 DOI: 10.1007/s12185-013-1373-1
    Studies of survival outcomes in acute myeloid leukemia (AML) patients treated with allogeneic haematopoietic stem cell transplantation (HSCT) are essential for planning patient care. The objectives of the present study were to determine overall survival (OS) and disease-free survival (DFS) in AML patients treated with allogeneic HSCT, and to identify prognostic factors associated with poor outcome. This study was conducted retrospectively, using data from the Blood and Bone Marrow Transplant, National Transplant Registry, Malaysia. All cases of AML treated with allogeneic HSCT registered at the registry between 1st January 1987 and 31st December 2010 were included in the study. A total of 300 patients were included for final analysis. The Kaplan-Meier method and Cox proportional hazard regression were used for statistical analysis. The overall 10-year OS and DFS for Malaysian AML patients after allogeneic HSCT were 63 and 67 %, respectively. Donor gender, marrow status, and conditioning intensity were identified as important prognostic factors for overall survival, whereas the significant prognostic factors for disease-free survival were ethnic group, donor gender, marrow status, and conditioning intensity. In conclusion, the survival outcomes for Malaysian AML patients treated with allogeneic HSCT were good, and this treatment should be considered the standard therapeutic approach for suitable candidates.
    Matched MeSH terms: Leukemia, Myeloid, Acute/mortality*; Leukemia, Myeloid, Acute/therapy*
  14. Surveillance blood counts for early detection of relapse in acute lymphoblastic leukemia
    Ariffin H, Lim HL
    Pediatr Blood Cancer, 2005 Aug;45(2):229.
    PMID: 15768379
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
  15. Fulltext Sudden visual loss in acute leukaemia
    Tengku Kamalden, T.A., Nurliza, K., Haris, A.R.
    JUMMEC, 2008;11(1):30-32.
    MyJurnal
    The presenting signs of acute leukaemia occur as a result of bone marrow failure and organ infiltration. Increased bleeding tendencies are seen on the skin, gums and mucosal lining. Bleeding in the posterior segment of the eye, namely the retina and vitreous, may occur, but do not usually cause any visual disturbances. This case demonstrates visual loss as a result of premacular subhyaloid haemorrhage in acute leukaemia.
    Matched MeSH terms: Leukemia
  16. Fulltext Successful treatment of Candida albicans endocarditis in a child with leukemia--a case report and review of the literature
    Ariffin H, Ariffin W, Tharam S, Omar A, de Bruyne J, Lin HP
    Singapore Med J, 1999 Aug;40(8):533-6.
    PMID: 10572495
    Candida species is now being increasingly recognised as an important cause of endocarditis especially in immunocompromised patients. A case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia (ALL) is reported. The child did not have a central venous catheter at any time. Treatment consisted of intravenous amphotericin B and fluconazole for 3 weeks followed by oral fluconazole for 2 weeks. No surgical resection was necessary. We highlight here the importance of echocardiography in the management of prolonged febrile neutropenia and discuss the dilemma of continuing chemotherapy in such patients.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
  17. Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study
    Oh BLZ, Lee SHR, Foo KM, Chiew KH, Seeto ZZL, Chen ZW, et al.
    Eur J Cancer, 2021 01;142:92-101.
    PMID: 33246161 DOI: 10.1016/j.ejca.2020.10.010
    In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.

    PATIENTS AND METHODS: We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes.

    RESULTS: The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p 

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
  18. Fulltext Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis
    Ngiow Shin Foong, Maha Abdullah, Jasmine Lim, Cheong Soon-Keng, Seow Heng-Fong
    Malaysian Journal of Medicine and Health Sciences, 2016;12(1):19-31.
    MyJurnal
    Introduction: Current prognostic markers have improved survival prediction, however, it has not
    advanced treatment strategies. Gene expression profiling may identify biological markers suitable as
    therapeutic targets. Leukaemia stem cell is associated with adverse outcome, however, its biological
    characteristics are still being investigated. We observed higher in vitro cell viability in acute myeloid
    leukaemia (AML) samples with poor prognosis, which may be stem cell related. Objective: The
    objective of this study was to profile highly expressed genes in an AML sample of poor prognosis/high
    viability and compare with a sample of good prognosis/low viability. Method: Subtractive hybridization
    was performed on two AML samples with high blast counts (>80%), a poor prognosis, PP (disease free
    survival, DFS12 months) sample. The PP sample had
    higher CD34+ counts (73% vs 46%) and higher cell viability than the GP sample. cDNA libraries were
    subsequently cloned and sequenced. Results: cDNA subtracted from the PP samples was identified
    as genes active during fetal/embryonic development (LCOR, CNOT1, ORMDL1), HOX- related genes
    (HOXA3, PBX3, SF3B1), hematopoiesis (SELL, IL-3RA) and aerobic glycolysis/hypoxia (PGK1,
    HIGD1A) -associated genes. Majority of GP clones isolated contained genes involved in oxidative
    phosphorylation, OXPHOS (COXs, ATPs, MTND4 and MTRNR2), protein synthesis (including
    ribosomal proteins, initiating and elongation factors), chromatin remodeling (H2AFZ, PTMA), cell
    motility (MALAT1, CALM2, TMSB4X), and mitochondria (HSPA9, MPO) genes. Conclusion: Thus,
    the PP sample exhibited stem cell-like features while the GP sample showed cells at a high level of cell
    activity. These genes are potential prognostic markers and targets for therapy.
    Matched MeSH terms: Leukemia
  19. Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation
    Orlikova B, Schumacher M, Juncker T, Yan CC, Inayat-Hussain SH, Hajjouli S, et al.
    Food Chem Toxicol, 2013 Sep;59:572-8.
    PMID: 23845509 DOI: 10.1016/j.fct.2013.06.051
    (R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 μM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 μM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.
    Matched MeSH terms: Leukemia/drug therapy*
  20. Streptokinase infusion for asparaginase-induced arterial thrombosis
    Omar KZ, Ariffin H, Abdullah WA, Chan LL, Lin HP
    Med. Pediatr. Oncol., 2000 May;34(5):377-8.
    PMID: 10797367
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
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