Displaying publications 61 - 80 of 464 in total

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  1. Erythrocarpines A-E, new cytotoxic limonoids from Chisocheton erythrocarpus
    Awang K, Lim CS, Mohamad K, Morita H, Hirasawa Y, Takeya K, et al.
    Bioorg Med Chem, 2007 Sep 1;15(17):5997-6002.
    PMID: 17576066
    Five new cytotoxic limonoids, erythrocarpines A-E (1-5), were isolated from the bark of Chisocheton erythrocarpus Hiern. Chemical structures, stereochemistry, and conformation were fully elucidated and characterized by 2D NMR, MS, and computational methods.
    Matched MeSH terms: Leukemia/pathology
  2. Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2
    Gapil Tiamas S, Daressy F, Abou Samra A, Bignon J, Steinmetz V, Litaudon M, et al.
    Bioorg Med Chem Lett, 2020 04 01;30(7):127003.
    PMID: 32035700 DOI: 10.1016/j.bmcl.2020.127003
    A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
    Matched MeSH terms: Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors*
  3. Fulltext Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations
    Hu S, Qian M, Zhang H, Guo Y, Yang J, Zhao X, et al.
    Blood, 2017 06 15;129(24):3264-3268.
    PMID: 28408461 DOI: 10.1182/blood-2017-03-771162
    Matched MeSH terms: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  4. Fulltext Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry
    Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al.
    Blood, 2017 Sep 07;130(10):1209-1212.
    PMID: 28659275 DOI: 10.1182/blood-2017-05-782383
    Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  5. Fulltext Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia
    Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, et al.
    Blood Adv, 2021 12 14;5(23):5226-5238.
    PMID: 34547766 DOI: 10.1182/bloodadvances.2021004895
    Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  6. 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*
  7. Second haploidentical peripheral blood stem cell transplantation for treatment of acute leukemia with relapse after first allogeneic peripheral blood stem cell transplantation
    Yeh SP, Lin CC, Lin CH, Lo WC, Chen TT, Lo WJ, et al.
    Bone Marrow Transplant, 2015 Jul;50(7):1001-3.
    PMID: 25867646 DOI: 10.1038/bmt.2015.67
    Matched MeSH terms: Leukemia/therapy*
  8. Fulltext Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric acute lymphoblastic leukaemia
    Lu Y, Kham SK, Ariffin H, Oei AM, Lin HP, Tan AM, et al.
    Br. J. Cancer, 2014 Mar 18;110(6):1673-80.
    PMID: 24434428 DOI: 10.1038/bjc.2014.7
    Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  9. Fulltext Circulating cytokines and small molecules follow distinct expression patterns in acute myeloid leukaemia
    Islam M, Mohamed EH, Esa E, Kamaluddin NR, Zain SM, Yusoff YM, et al.
    Br. J. Cancer, 2017 Nov 07;117(10):1551-1556.
    PMID: 28898234 DOI: 10.1038/bjc.2017.316
    BACKGROUND: Although aberrant expression of cytokines and small molecules (analytes) is well documented in acute myeloid leukaemia (AML), their co-expression patterns are not yet identified. In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML.

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

    RESULTS: In our study, 16 analytes are found to be significantly deregulated (13 higher, 3 lower, Mann-Whitney U-test, P-value <0.005), where 5 of them have never been reported before in AML. We predicted a seven-analyte-containing multiplex panel for diagnosis of AML and, among them, MIF could be a possible therapeutic target. In addition, we observed that circulating analytes show five co-expression signatures.

    CONCLUSIONS: Circulating analyte expression in AML significantly differs from normal, and follow distinct expression patterns.

    Matched MeSH terms: Leukemia, Myeloid, Acute/blood*
  10. Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B-lymphoblastic leukaemia: Ma-Spore ALL 2010 study
    Jiang N, Wang L, Xiang X, Li Z, Chiew EKH, Koo YM, et al.
    Br J Clin Pharmacol, 2021 Apr;87(4):1990-1999.
    PMID: 33037681 DOI: 10.1111/bcp.14596
    AIMS: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.

    METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.

    RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.

    CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

    Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
  11. Macular haemorrhage in adult acute leukaemia patients at presentation and the risk of subsequent intracranial haemorrhage
    Jackson N, Reddy SC, Harun MH, Quah SH, Low HC
    Br J Haematol, 1997 Jul;98(1):204-9.
    PMID: 9233585
    Retinal changes are common in adult acute leukaemia patients at presentation, but whether they correlate with the risk of subsequent intracranial haemorrhage is unknown. A 4-year study has been carried out in 82 newly-diagnosed acute leukaemia patients, aged 12-77 years, who were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without these features were compared for their risk of intra-cranial haemorrhage (ICH) within the first 30 d following diagnosis. There was no association between the incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95% [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis, MH remained a highly significant risk factor for ICH. Patients with MH should be monitored intensively for the development of ICH, and receive priority in the allocation of platelets where these are in short supply.
    Matched MeSH terms: Leukemia, Myeloid/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*
  12. Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy
    Jackson N, Shukri A, Ali K
    Br J Haematol, 1993 Sep;85(1):203-4.
    PMID: 8251394
    A patient being treated for chronic myeloid leukaemia with hydroxyurea became pregnant. Despite an increase in the dose of hydroxyurea (to 3 g per day) during the pregnancy, her white blood cell count could only be controlled at about 150 x 10(9)/l. A healthy baby girl was born at 37 weeks with normal blood counts and no evidence of congenital abnormality. There are now five reports of the use of hydroxyurea in pregnancy, and where leukapheresis is not available it may be the treatment of choice.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
  13. Treating childhood acute myeloid leukaemia with the AML-BFM-83 protocol: experience in a developing country
    Chan LL, Abdel-Latif ME, Ariffin WA, Ariffin H, Lin HP
    Br J Haematol, 2004 Sep;126(6):799-805.
    PMID: 15352983
    Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.
    Matched MeSH terms: Leukemia, Myeloid/drug therapy*
  14. Stomatocytic elliptocytosis and 'neutrophil drumsticks' as a marker of stem cell engraftment
    S-Abdul-Wahid F, Soon-Keng C
    Br J Haematol, 2002 Mar;116(4):731.
    PMID: 11886374
    Matched MeSH terms: Leukemia, Myeloid/pathology*
  15. Mature B-cell acute lymphoblastic leukaemia associated with a rare MLL-FOXO4 fusion gene
    Lim L, Chen KS, Krishnan S, Gole L, Ariffin H
    Br J Haematol, 2012 Jun;157(6):651.
    PMID: 22429121 DOI: 10.1111/j.1365-2141.2012.09091.x
    Matched MeSH terms: Leukemia, B-Cell/genetics*; Leukemia, B-Cell/metabolism; Leukemia, B-Cell/pathology; Myeloid-Lymphoid Leukemia Protein/genetics*; Myeloid-Lymphoid Leukemia Protein/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
  16. Hypercalcaemia: an unusual presenting feature of childhood acute lymphoblastic leukaemia
    Rajagopal R, Lum SH, Jalaludin MY, Krishnan S, Abdullah WA, Ariffin H
    Br J Haematol, 2013 Oct;163(2):147.
    PMID: 23961807 DOI: 10.1111/bjh.12500
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
  17. Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling
    Yeoh AE, Li Z, Dong D, Lu Y, Jiang N, Trka J, et al.
    Br J Haematol, 2018 Jun;181(5):653-663.
    PMID: 29808917 DOI: 10.1111/bjh.15252
    Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10-3 ). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03-16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10-3 ). We conclude that our novel metric - ERM-D8 - based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  18. Clinical stage of chronic granulocytic leukaemia and BCR breakpoint location in South-East Asian patients
    Dyck JA, Bosco JJ
    Br J Haematol, 1989 May;72(1):64-7.
    PMID: 2736243
    Forty-six Malaysian patients with chronic granulocytic leukaemia were found to be rearranged in the breakpoint cluster region (BCR) of chromosome 22, molecular evidence of Philadelphia chromosome (t9.22) translocation. Through the use of a 1.2 kb 3' BCR probe and two restriction enzyme digests, patients' breakpoints could be localized either to 5' or 3' regions of the BCR. Breakpoint site localization at the time of DNA sampling did not show any positive statistical association to clinical status defined as chronic phase, chronic phase with less than 6 months to blast crisis, accelerated phase and blast crisis. This was in contrast to earlier reports which indicated that patients with breakpoint at 3' site were at a higher biologic risk for entering blast crisis.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*
  19. Fulltext Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd
    Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.
    Br J Haematol, 2017 10;179(2):219-228.
    PMID: 28699641 DOI: 10.1111/bjh.14829
    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology
  20. Fulltext Cytogenetics and molecular genetic tests for the diagnosis and treatment of chronic myeloid leukemia
    Mohd Khairi Zahry, Ankathil, Ravindran
    Buletin Persatuan Genetik Malaysia, 2008;14(1):9-11.
    MyJurnal
    Chronic Myeloid Leukemia (CML) is a clonal disorder thought to originate in a single abnormal haematopoietic stem cell. This myeloproliferative fatal stem cell disorder comprises
    approximately 14% of all leukemias. In most cases, CML runs a triphasic course, which includes an initial chronic phase that transforms eventually into a blastic phase resembling acute leukemia. In 60%- 80% of patients, an intermediate or accelerated phase precedes the terminal blastic phase. Accelerated phase and blastic phase sometimes are lumped together and considered to be
    advanced phase CML. The entire continuum from chronic phase to blastic phase lasts a median of 3 to 5 years . This time period can be broken down in to the chronic phase which if untreated,
    lasts for 2 to 5 years and finally the fatal blastic phase, which lasts from 3 to 6 months. A patient can present in any of these 3 stages.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
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