Displaying publications 1 - 20 of 67 in total

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  1. 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.
  2. Fulltext Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman
    Yousuf R, Mustafa AN, Ho SL, Tang YL, Leong CF
    Asian J Transfus Sci, 2017 3 21;11(1):62-64.
    PMID: 28316444 DOI: 10.4103/0973-6247.200770
    The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.
  3. Fulltext Extended and stable gene expression via nucleofection of MIDGE construct into adult human marrow mesenchymal stromal cells
    Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O
    Cytotechnology, 2012 Mar;64(2):203-16.
    PMID: 22160354 DOI: 10.1007/s10616-011-9413-2
    Human mesenchymal stromal cell (hMSC) is a potential target for cell and gene therapy-based approaches against a variety of different diseases. Whilst cationic lipofection has been widely experimented, the Nucleofector technology is a relatively new non-viral transfection method designed for primary cells and hard-to-transfect cell lines. Herein, we compared the efficiency and viability of nucleofection with cationic lipofection, and used the more efficient transfection method, nucleofection, to deliver a construct of minimalistic, immunologically defined gene expression encoding the erythropoietin (MIDGE-EPO) into hMSC. MIDGE construct is relatively safer than the viral and plasmid expression systems as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. Using a plasmid encoding the luciferase gene, we demonstrated a high transfection efficiency using the U-23 (21.79 ± 1.09%) and C-17 (5.62 ± 1.09%) pulsing program in nucleofection. The cell viabilities were (44.93 ± 10.10)% and (21.93 ± 5.72)%, respectively 24 h post-nucleofection. On the other hand, lipofection treatment only yielded less than 0.6% efficiencies despite showing higher viabilities. Nucleofection did not affect hMSC renewability, immunophenotype and differentiation potentials. Subsequently, we nucleofected MIDGE-EPO using the U-23 pulsing program into hMSC. The results showed that, despite a low nucleofection efficiency with this construct, the EPO protein was stably expressed in the nucleofected cells up to 55 days when determined by ELISA or immunocytochemical staining. In conclusion, nucleofection is an efficient non-viral transfection approach for hMSC, which when used in conjunction with a MIDGE construct, could result in extended and stable transgene expression in hMSC.
  4. In vitro expression of erythropoietin by transfected human mesenchymal stromal cells
    Mok PL, Cheong SK, Leong CF, Othman A
    Cytotherapy, 2008;10(2):116-24.
    PMID: 18368590 DOI: 10.1080/14653240701816996
    Mesenchymal stromal cells (MSC) are pluripotent progenitor cells that can be found in human bone marrow (BM). These cells have low immunogenicity and could suppress alloreactive T-cell responses. In the current study, MSC were tested for their capacity to carry and deliver the erythropoietin (EPO) gene in vitro.
  5. Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro
    Choong PF, Mok PL, Cheong SK, Leong CF, Then KY
    Cytotherapy, 2007;9(2):170-83.
    PMID: 17453969
    The multipotency of stromal cells has been studied extensively. It has been reported that mesenchymal stromal cells (MSC) are capable of differentiating into cells of multilineage. Different methods and reagents have been used to induce the differentiation of MSC. We investigated the efficacy of different growth factors in inducing MSC differentiation into neurons.
  6. Cell viability of acute myeloid leukaemia blasts in culture correlates with treatment outcome
    Maha A, Cheong SK, Leong CF, Seow HF
    Hematology, 2008 Feb;13(1):13-20.
    PMID: 18534060 DOI: 10.1179/102453308X315762
    Despite the advances in understanding the pathophysiology of acute myeloid leukaemia (AML), the cure rate for acute myeloid leukaemia patients remains low. Cytogenetic abnormalities and age are the prognostic factors that guide treatment decisions. However, many AML patients still die. The biological factors that influence treatment outcome are largely unknown. Thus, the objective of our study was to use the in vitro viability test to correlate with treatment outcome. Acute myeloid leukaemia blasts demonstrated differing ability to survive in culture. Our examination of blast phenotype at various days in culture showed two possible growth directions. First, cells underwent maturation by increased expression of CD16 and down-regulated CD34 (a haemopoietic stem cell marker). These cells also appeared to have undergone apoptosis. Alternatively, cells continued to survive in culture and maintained high expression of CD34. An MTT assay was carried out to determine viability after three days of culture. Lower optical density values were obtained for samples that underwent apoptosis and higher values were obtained for samples that survived in culture. Apoptosis was measured by Annexin V/propidium iodide staining. A comparison between results of MTT assay and duration of disease free survival revealed that a higher viability in vitro correlated significantly with shorter survival duration in the patient (R -0.761, p=0.002, n=13). Thus, this study further supports the hypothesis that AML patients with poor survival may be related to having blasts with a biologically more immature or stem cell-like nature.
  7. Relapsed non-Hodgkin's lymphoma with high CA-125 mimicking ovarian tumour
    Leong CF, Cheong SK, Ng P, Amran AR
    Hosp Med, 2003 Nov;64(11):686-7.
    PMID: 14671884
  8. Fulltext Incidence of Red Cell Alloantibody among the Transfusion Recipients of Universiti Kebangsaan Malaysia Medical Centre
    Yousuf R, Abdul Aziz S, Yusof N, Leong CF
    Indian J Hematol Blood Transfus, 2013 Jun;29(2):65-70.
    PMID: 24426338 DOI: 10.1007/s12288-012-0155-x
    Red blood cell alloimmunization is a common complication among the transfusion recipients. In Malaysia, multiple ethnicity causes genetic heterogeneity among the population which in turn can cause a wide variation of antibody. The objective of this study was to analyse the red cell alloantibody detected during the pre-transfusion testing. This was a cross-sectional study done in the blood bank of Universiti Kebangsaan Malaysia Medical Centre during the period of January-December 2010. The data was retrieved from the hospital laboratory information system. A total of 24,263 patients' blood samples were subjected for pre-transfusion testing. Antibody screening was done using an indirect antiglobulin test method. The positive samples were further identified for antibody specificity. Antibody screening tests were positive in 184 patients out of 24,263 samples with the incidence of 0.76 %. Autoantibodies and alloantibodies were detected in 39/184 (21.2 %) and 140/184 (76.1 %) of the patients respectively. In five patients (2.7 %) the antibody specificity remained undetermined. Total 161 alloantibodies were identified. The suspected Anti-Mia alloantibody was observed most frequently (49/161, 30.4 %) followed by anti-E (30/161, 18.6 %) and anti-D (22/161, 13.7 %). Anti-E and anti-c were the most common combination of multiple alloantibodies. In view of the high incidence of suspected Anti-Mia antibodies, more efforts are needed to look into the techniques for confirmation of the Anti-Mia antibodies. Besides that, we suggested that all multiply transfused patients should be phenotyped for the Rh system and to supply Rh phenotype specific blood in order to limit alloimmunization.
  9. Fulltext A Preliminary Study on Coagulation Parameters and Sterility of Thawed Refrozen Fresh Frozen Plasma
    Draman R, Yousuf R, Abdul Aziz S, Ding CH, Zainol S, Leong CF
    Indian J Hematol Blood Transfus, 2020 Jan;36(1):112-116.
    PMID: 32174694 DOI: 10.1007/s12288-019-01171-0
    Thawed fresh frozen plasma (FFP) if not used within 6 h, may have to be discarded due to the risk of contamination and uncertainty about its quality. The main objective of this study was to evaluate the levels of coagulation Factor II (FII), Factor VIII (FVIII), fibrinogen and bacterial growth in thawed refrozen FFP. Thirty FFP samples were collected from healthy donors. FFP were thawed in water bath at 37 °C for 20-25 min. Approximately 10 mL of plasma from each FFP unit was tested for FII, FVIII, fibrinogen and sterility. The thawed FFP units were then kept at 4 °C for 6 h before being refrozen and stored at - 20 °C. Two weeks later, the refrozen FFP were thawed again and representative samples were analysed as before. There was a significant decline in the mean FVIII level, from 155.77% to 85.6% at second thaw. The mean FII level increased significantly from 74.9% to 82%, whereas the mean fibrinogen level fell from 3.34g/L to 3.28 g/L, but the decline was not statistically significant. There was no bacterial contamination in all samples at both time points. Refrozen plasma may be considered as an alternative to the storage of thawed unused FFP provided they are kept in a controlled environment to reduce wastage. These thawed refrozen FFP can be used later in bleeding cases like other FFP as the levels of FVIII are still within the standard haematology range (0.5-2 IU/mL) and above the minimal level of 30% coagulation factors required for adequate haemostasis.
  10. Fulltext A rare case of anti-jk3 antibody detected on pre-transfusion investigation
    Yousuf R, Abdul Aziz S, Yusof N, Leong CF
    Indian J Hematol Blood Transfus, 2014 Sep;30(3):208-10.
    PMID: 25114411 DOI: 10.1007/s12288-012-0211-6
    We report a 47-year-old Malay lady, para 4 + 1, with known medical history of hypertension whom presented at Emergency Department with severe anaemia, most likely secondary to menorrhagia caused by uterine fibroids. Her haemoglobin was 5.5 g/dl and she was transfused with three units of packed cell without any adverse reaction, her haemoglobin level increased to 9.8 g/dl. She was then planned for total abdominal hysterectomy and bilateral salpingo-oophorectomy later. Four months later when she came for the elective surgery, her pre transfusion investigations showed blood group as B Rh D positive, with a probable R1R1 phenotype. Her antibody screening was positive in all the three panel cells. Further testings showed a negative Direct Coomb's test and negative autocontrol, antibody identification showed pan-agglutination reaction on all 11 panel cells with enzyme enhancement. Patient's red cell phenotype was Jk(a-b-). Anti-Jk3 was suspected and further confirmed in the reference laboratory by phenotyping as well as negative urea lysis test. This case report highlights an extremely rare but clinically significant anti-JK3 antibody detected during pretransfusion testing. This phenotype is rare in the white population, more commonly seen in various polynesians. Increased awareness among the blood bank personnel regarding the variability of the blood group phenotype and the capricious nature of the Kidd antibodies may contribute to the better management of these patients.
  11. Correction to: Systematic review of pre-clinical chronic myeloid leukaemia
    Kuan JW, Su AT, Leong CF, Osato M, Sashida G
    Int J Hematol, 2019 Jan;109(1):130.
    PMID: 30406326 DOI: 10.1007/s12185-018-2556-6
    The author would like to correct the error in the publication of the original article. The corrected detail is given below for your reading.
  12. 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.

  13. Pegylated granulocyte-colony stimulating factor versus non-pegylated granulocyte-colony stimulating factor for peripheral blood stem cell mobilization: A systematic review and meta-analysis
    Kuan JW, Su AT, Leong CF
    J Clin Apher, 2017 Dec;32(6):517-542.
    PMID: 28485020 DOI: 10.1002/jca.21550
    Granulocyte-colony stimulating factor (G-CSF) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood, enabling its harvest by few apheresis procedures. The pegylated G-CSF has longer half-life and is given once only, which is more comfortable for patients, whereas the non-pegylated requires multiple daily injection because of its short half-life. We summarized results of randomized trials comparing the efficacy and safety of pegylated and non-pegylated G-CSF for peripheral blood stem cell mobilization. We searched the Cochrane CENTRAL, MEDLINE, EMBASE, and two conference proceedings. Two authors made the selection, extracted data and evaluated methodological quality using GRADE independently. We used random-effects model for meta-analysis. We found 3956 records and retrieved 47 full texts. We included eight randomized trials with a total number of 554 randomized and 532 analyzed subjects. The meta-analysis included five trials because not all trials reported the same outcomes. Pooling data from two studies shows no evidence for a difference in the successful mobilization rate (CD34+ cell ≥ 2 × 106 /kg collected) between pegfilgrastim 6 mg (early administration) and filgrastim 5 µg/kg/day (147 participants; risk ratio (RR) 0.87, 95% confidence interval (95%CI) 0.67-1.11; P = .26). Pooling data from three studies shows no difference in the incidence of adverse events between pegylated and non-pegylated G-CSF (170 participants; RR 0.86, 95%CI 0.34-2.17; P = .75). No difference found on the quantity of CD34+ cells collected, number of apheresis procedure in successful mobilization, level of peak PB CD34+ cells achieved, and day of neutrophil and platelet engraftment.
  14. Fulltext Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report
    Yousuf R, Abdul Aziz S, Yusof N, Leong CF
    J Med Case Rep, 2012;6:71.
    PMID: 22348809 DOI: 10.1186/1752-1947-6-71
    Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD)-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization.
  15. ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency presenting as hydrops foetalis
    Suria AA, Nurasyikin Y, Adibah AG, Cheah FC, Leong CF
    Clin Ter, 2014;165(3):151-4.
    PMID: 24999569 DOI: 10.7417/CT.2014.1714
    ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency G6PD are common haematological problems affecting the newborn. The resulting haemolytic disease of foetus and newborn (HDFN) caused by either of these pathologies generally follows a benign course. It is typically characterized by mild jaundice without significant anaemia. ABO incompatibility alone as a cause of foetal hydrops is extremely rare. We report a case of a newborn baby girl with an anti-B isoimmunisation and G6PD deficiency manifesting with hydrops foetalis, anaemia and hyperbilirubinaemia, born to a mother with blood group O.
  16. Role of blood bag temperature indicators in maintaining patent temperature of the returned unused blood bags in blood bank
    Nurasyikin Y, Leong CF, Fadhlullah TM, Hafiz WM, Nadiah Z, Atieqah AN, et al.
    Clin Ter, 2011;162(1):19-22.
    PMID: 21448541
    The main objective of the present study was to evaluate the temperature chain of red blood cells (RBC) returned unused blood bags using blood temperature indicator and ascertain the factors like transportation time, type, size of coolant box and number of bags per box.
  17. Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
    Teoh HK, Chong PP, Abdullah M, Sekawi Z, Tan GC, Leong CF, et al.
    Leuk. Res., 2016 Jan;40:44-53.
    PMID: 26626206 DOI: 10.1016/j.leukres.2015.10.004
    Studies demonstrated that mesenchymal stromal cells (MSC) from bone marrow stroma produced high concentration of interleukin-6 (IL-6) that promoted multiple myeloma cell growth. In view of the failure of IL-6 monoclonal antibody therapy to demonstrate substantial clinical responses in early clinical trials, more effective methods are needed in order to disrupt the favourable microenvironment provided by the bone marrow stroma. In this study, we evaluated the short interfering RNA (siRNA)-mediated silencing of IL-6 in MSC and the efficacy of these genetically modified MSC, with IL-6 suppression, on inhibition of U266 multiple myeloma cell growth. IL-6 mRNA and protein were significantly suppressed by 72h post IL-6 siRNA transfection without affecting the biological properties of MSC. Here we show significant inhibition of cell growth and IL-6 production in U266 cells co-cultured with MSC transfected with IL-6 siRNA when compared to U266 cells co-cultured with control MSC. We also show that the tumour volume and mitotic index of tumours in nude mice co-injected with U266 and MSC transfected with IL-6 siRNA were significantly reduced compared to tumours of mice co-injected with control MSC. Our results suggest potential use of RNA interference mediated therapy for multiple myeloma.
  18. MicroRNAs that affect the Fanconi Anemia/BRCA pathway are downregulated in imatinib-resistant chronic myeloid leukemia patients without detectable BCR-ABL kinase domain mutations
    Yap E, Norziha ZA, Simbun A, Tumian NR, Cheong SK, Leong CF, et al.
    Leuk. Res., 2017 08;59:32-40.
    PMID: 28544907 DOI: 10.1016/j.leukres.2017.05.015
    Chronic myeloid leukemia (CML) patients who do not achieve landmark responses following treatment with imatinib mesylate (IM) are considered IM-resistant. Although IM-resistance can be due to BCR-ABL kinase domain (KD) mutations, many IM-resistant patients do not have detectable BCR-ABL KD mutations. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression. To investigate the role of miRNAs in IM-resistance, we recruited 8 chronic phase CML patients with IM-resistance who tested negative for BCR-ABL KD mutations and 2 healthy normal controls. Using miRNA sequencing, we identified 54 differentially expressed miRNAs; 43 of them downregulated. The 3 most differentially downregulated miRNAs were miR-146a-5p, miR-99b-5p and miR-151a-5p. Using real-time quantitative reverse transcriptase-polymerase chain reaction, the expression patterns of the 3 miRNAs were validated on the same cohort of 8 patients in addition to 3 other IM-resistant CML patients. In-silico analysis showed that the predicted gene targets are ATRIP, ATR, WDR48, RAD51C and FANCA genes which are involved in the Fanconi Anemia/BRCA pathway. This pathway regulates DNA damage response (DDR) and influences disease response to chemotherapy. Thus it is conceivable that DDR constitutes a key component in IM-resistance. Further research is needed to elucidate miRNA modulation of the predicted gene targets.
  19. Fulltext S-phase fraction and pro-inflammatory cytokine expressions in acute lymphoblastic leukaemia
    Maha A, Cheong SK, Leong CF, Seow HF
    Malaysian Journal of Medicine and Health Sciences, 2005;1(1):41-51.
    Objective: Despite much progress in treatment strategies, long term survival of adult ALL is still inferior to that in children. The underlying mechanisms for these differences are largely unknown. Intensification of contemporary therapy has also resulted in many children being over-treated. The action of chemotherapeutic drugs used in the treatment of ALL includes cell cycle dependent agents which are effective on cells that are proliferating. Cell proliferation in haemopoietic cells is controlled by cytokines. Thus, we proposed to study the cell cycle profile of ALL cases and also expression of cytokines to determine their role in affecting treatment outcome in the different age groups.
    Methods: We determined the S-phase fraction from the cell cycle profile by flowcytometry and tested the expressions of cytokine IL-1beta, IL-6, IL-18, IFN-gamma, TNF-alpha and GM-CSF using RT-PCR in de novo ALL cases.
    Results: We found a significantly higher S-phase fraction in samples from children 2-10 years old compared to the older age group (>10 years old) (p=0.001). GM-CSF was found to be expressed in a significantly lower percentage of children compared to adults (p=0.008).
    Conclusion: Our results implied that GM-CSF may have induced cell cycle arrests in adult ALL resulting in a lower percentage of S-phase fraction. This may contribute to the poorer prognosis in adult ALL because non-cycling blasts are less sensitive to some chemotherapeutic drugs.
    Keywords: ALL, S-phase fraction, GM-CSF, age
  20. Fulltext Primary Thyroid Lymphoma: Two Different Presentations of a Rare Disease
    Azlin, I., Leong, CF, Hamidah, N.H., Sharifah, N.A., Isa, M.R., Rohaizak, M.
    Medicine & Health, 2010;5(2):114-119.
    MyJurnal
    Primary thyroid lymphoma is a rare disorder accounting for about 2% of all malignant lymphomas and less than 5% of thyroid malignancies. It is an aggressive disease with poor outcome. The majority of thyroid lymphomas are non-Hodgkin lymphomas of Bcell origin. Majority of cases occur in women in the sixth decade. We report two cases of primary thyroid lymphoma and highlight the clinical issues and challenges posed by this rare disease. Both cases presented with respiratory obstructive symptoms that required surgical intervention. The optimal management for a primary thyroid lymphoma be it chemotherapy, radiotherapy, surgery or monoclonal antibodies is still debatable. The role for surgery has evolved through the years but its importance in emergency situations should not be overlooked. Both our patients had to undergo surgery but only one patient received additional chemotherapy and radiotherapy. These two case reports illustrated the difficulties in managing this rare disorder.
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