Displaying publications 1 - 20 of 111 in total

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  1. Nadarajan VS, Phan CL, Ang CH, Liang KL, Gan GG, Bee PC, et al.
    Int J Hematol, 2011 Apr;93(4):465-473.
    PMID: 21387093 DOI: 10.1007/s12185-011-0796-9
    The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
    Matched MeSH terms: Leukemia, Myeloid, Accelerated Phase/drug therapy; Leukemia, Myeloid, Accelerated Phase/genetics; Leukemia, Myeloid, Chronic-Phase/drug therapy; Leukemia, Myeloid, Chronic-Phase/genetics
  2. Mat Yusoff Y, Abu Seman Z, Othman N, Kamaluddin NR, Esa E, Zulkiply NA, et al.
    Asian Pac J Cancer Prev, 2019 06 01;20(6):1749-1755.
    PMID: 31244296 DOI: 10.31557/APJCP.2019.20.6.1749
    Objective: The most frequent acquired molecular abnormalities and important prognostic indicators in patients
    with Acute Myeloid Leukaemia (AML) are fms-like tyrosine kinase-3 gene (FLT3) and nucleophosmin-1 (NPM1)
    mutations. Our study aims to develop a cost effective and comprehensive in-house conventional PCR method for
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations and to evaluate the frequency of these mutations in patients
    with cytogenetically normal (CN) AML in our population. Methods: A total of 199 samples from AML patients (95
    women, 104 men) were included in the study. Mutation analyses were performed using polymerase chain reaction
    (PCR) and gene sequencing. Result: Sixty-eight patients were positive for the mutations. FLT3-ITD mutations were
    detected in 32 patients (16.1%), followed by FLT3-D835 in 5 (2.5%) and NPM1 in 54 (27.1%). Double mutations of
    NPM1 and FLT3-ITD were detected in 23 cases (11.6%). Assays validation were performed using Sanger sequencing
    and showed 100% concordance with in house method. Conclusion: The optimized in-house PCR assays for the
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations in AML patients were robust, less labour intensive and cost
    effective. These assays can be used as diagnostic tools for mutation detection in AML patients since identification of
    these mutations are important for prognostication and optimization of patient care.
    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*; Leukemia, Myeloid, Acute/pathology
  3. 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*
  4. Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, et al.
    Genet Test Mol Biomarkers, 2021 Mar;25(3):199-210.
    PMID: 33734890 DOI: 10.1089/gtmb.2020.0182
    Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.
    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*
  5. Bashanfer SAA, Saleem M, Heidenreich O, Moses EJ, Yusoff NM
    Oncol Rep, 2019 Mar;41(3):2027-2040.
    PMID: 30569130 DOI: 10.3892/or.2018.6926
    The t(8;21) translocation is one of the most frequent chromosome abnormalities associated with acute myeloid leukaemia (AML). This abberation deregulates numerous molecular pathways including the ERK signalling pathway among others. Therefore, the aim of the present study was to investigate the gene expression patterns following siRNA‑mediated suppression of RUNX1‑RUNX1T1 and MAPK1 in Kasumi‑1 and SKNO‑1 cells and to determine the differentially expressed genes in enriched biological pathways. BeadChip microarray and gene ontology analysis revealed that RUNX1‑RUNX1T1 and MAPK1 suppression reduced the proliferation rate of the t(8;21) cells with deregulated expression of several classical positive regulator genes that are otherwise known to enhance cell proliferation. RUNX1‑RUNX1T1 suppression exerted an anti‑apoptotic effect through the overexpression of BCL2, BIRC3 and CFLAR genes, while MAPK1 suppression induced apopotosis in t(8;21) cells by the apoptotic mitochondrial changes stimulated by the activity of upregulated TP53 and TNFSF10, and downregulated JUN gene. RUNX1‑RUNX1T1 suppression supported myeloid differentiation by the differential expression of CEBPA, CEBPE, ID2, JMJD6, IKZF1, CBFB, KIT and CDK6, while MAPK1 depletion inhibited the differentiation of t(8;21) cells by elevated expression of ADA and downregulation of JUN. RUNX1‑RUNX1T1 and MAPK1 depletion induced cell cycle arrest at the G0/G1 phase. Accumulation of cells in the G1 phase was largely the result of downregulated expression of TBRG4, CCNE2, FOXO4, CDK6, ING4, IL8, MAD2L1 and CCNG2 in the case of RUNX1‑RUNX1T1 depletion and increased expression of RASSF1, FBXO6, DADD45A and P53 in the case of MAPK1 depletion. Taken together, the current results demonstrate that MAPK1 promotes myeloid cell proliferation and differentiation simultaneously by cell cycle progression while suppresing apoptosis.
    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*; Leukemia, Myeloid, Acute/pathology
  6. Ho CM, Khuzaiah R, Yasmin AM
    Med J Malaysia, 1994 Mar;49(1):29-35.
    PMID: 8057987
    Primary varicella-zoster virus infection in children with haematological malignancy is a life threatening disease. In one year, there were 10 cases of varicella and 2 cases of zoster among these children as well as 5 mothers who were accompanying their children who developed varicella in the oncology ward. Two children died of fulminating disease despite aggressive antiviral and supportive treatment. Acyclovir can be used in treatment and prophylaxis in exposed susceptible children. Varicella -zoster immune globulin is not available in this country. Vaccination with live virus has been shown to be protective in immunocompromised children and needs consideration.
    Matched MeSH terms: Leukemia, Myeloid/complications*
  7. 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
  8. Wong KK, Hassan R, Yaacob NS
    Front Oncol, 2021;11:624742.
    PMID: 33718188 DOI: 10.3389/fonc.2021.624742
    Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. Treatment of AML and MDS patients with the HMAs confers upregulation of cancer/testis antigens (CTAs) expression including the highly immunogenic CTA NY-ESO-1. This leads to activation of CD4+ and CD8+ T cells for elimination of cancer cells, and it establishes the feasibility to combine cancer vaccine with HMAs to enhance vaccine immunogenicity. Moreover, decitabine and guadecitabine induce the expression of immune checkpoint molecules in AML cells. In this review, the accumulating knowledge on the immunopotentiating properties of decitabine and guadecitabine in AML and MDS patients are presented and discussed. In summary, combination of decitabine or guadecitabine with NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients. T cells from AML patients stimulated with dendritic cell (DC)/AML fusion vaccine and guadecitabine display increased capacity to lyse AML cells. Moreover, decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor-engineered T cells antileukemic activities against AML. Furthermore, combination of either HMAs with immune checkpoint blockade (ICB) therapy may circumvent their resistance. Finally, clinical trials of either HMAs combined with cancer vaccines, NK cell infusion or ICB therapy in relapsed/refractory AML and high-risk MDS patients are currently underway, highlighting the promising efficacy of HMAs and immunotherapy synergy against these malignancies.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  9. Goh KL, Bosco J, Wong CS
    Med J Malaysia, 1983 Sep;38(3):194-6.
    PMID: 6584709
    Matched MeSH terms: Leukemia, Myeloid/blood; Leukemia, Myeloid/complications*
  10. 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*
  11. Kuan JW, Ng SY, Hon SL, Lim SM, Chai AJM, Teo HG, et al.
    Int J Lab Hematol, 2023 Feb;45(1):e1-e5.
    PMID: 35896146 DOI: 10.1111/ijlh.13940
    Matched MeSH terms: Leukemia, Myeloid*
  12. Zainul Abidin FN, Westhead DR
    Nucleic Acids Res, 2017 04 20;45(7):e53.
    PMID: 27994031 DOI: 10.1093/nar/gkw1270
    Clustering is used widely in 'omics' studies and is often tackled with standard methods, e.g. hierarchical clustering. However, the increasing need for integration of multiple data sets leads to a requirement for clustering methods applicable to mixed data types, where the straightforward application of standard methods is not necessarily the best approach. A particularly common problem involves clustering entities characterized by a mixture of binary data (e.g. presence/absence of mutations, binding, motifs and epigenetic marks) and continuous data (e.g. gene expression, protein abundance, metabolite levels). Here, we present a generic method based on a probabilistic model for clustering this type of data, and illustrate its application to genetic regulation and the clustering of cancer samples. We show that the resulting clusters lead to useful hypotheses: in the case of genetic regulation these concern regulation of groups of genes by specific sets of transcription factors and in the case of cancer samples combinations of gene mutations are related to patterns of gene expression. The clusters have potential mechanistic significance and in the latter case are significantly linked to survival. The method is available as a stand-alone software package (GNU General Public Licence) from http://github.com/BioToolsLeeds/FlexiCoClusteringPackage.git.
    Matched MeSH terms: Leukemia, Myeloid, Acute/genetics
  13. Menon BS, Wan Maziah WM
    Malays J Pathol, 2001 Jun;23(1):47-8.
    PMID: 16329548
    The aim of this study was to determine the incidence and outcome of herpes zoster hospitalised children with cancer in Kota Baru. It was a retrospective review from January 1994 to December 1998. The diagnosis of herpes zoster was a clinical one. Herpes zoster was diagnosed in 10 of 188 (5%) children with malignancy. The most common malignancy was leukaemia. Nine children were treated with acyclovir. No child developed visceral dissemination and there were no deaths.
    Matched MeSH terms: Leukemia, Myeloid, Acute/immunology; Leukemia, Myeloid, Acute/epidemiology; Leukemia, Myeloid, Acute/virology*
  14. Ng KP, Soo-Hoo TS, Na SL, Gan GG, Sangkar JV, Teh AKH
    Med J Malaysia, 2003 Oct;58(4):608-12.
    PMID: 15190640
    Scopulariopsis brevicaulis is a soil fungus normally associated with onychomycosis. It causes subcutaneous infection in immunocompromised patients and is rarely isolated from blood. A case of systemic Scopulariopsis brevicaulis infection was reported in a patient with acute myeloid leukemia. The patient developed persistent fever that did not respond to wide spectrum antibiotics and amphotericin B. Scopulariopsis brevicaulis was the only pathogen isolated from blood cultures. The fever subsided with itraconazole and there was no recurrence of fungal infection with prolonged maintenance of oral itraconazole.
    Matched MeSH terms: Leukemia, Myeloid/complications*
  15. Hassan H, Teh A
    Singapore Med J, 1994 Apr;35(2):217-8.
    PMID: 7939827
    Clostridium septicum infection has been shown to have a strikingly high association with either bowel or blood malignancies. The infection may be fatal if unrecognised. We report a case of C. septicum bacteremia in a man diagnosed with acute myeloid leukaemia.
    Matched MeSH terms: Leukemia, Myeloid, Acute/complications*; Leukemia, Myeloid, Acute/microbiology
  16. Gudum HR, Chin YM, Menaka N, Jeyaranee S, Lin HP, Tay A
    Malays J Pathol, 1992 Jun;14(1):25-8.
    PMID: 1469914
    Immunophenotypic studies using immunofluorescent flow cytometry were performed on the blast cells of 36 patients with acute leukaemia using a panel of eight monoclonal antibodies. Six patients had blasts which co-expressed markers for lymphoid and myeloid differentiation, and which were therefore defined as biphenotypic hybrid acute leukaemia. Of the six, three patients were in the paediatric age group (below 12 years old) while the other three were more than 12 years old. Peripheral blood counts were variable; however, bone marrow infiltration was extensive (blasts > or = 75% in all). At the time of study, remission was achieved in only two patients. The authors' data show that biphenotypic hybrid acute leukaemia is not rare in Malaysia. This represents a subgroup of acute leukaemia identifiable by immunophenotyping but not by the French-American-British classification based on morphological and basic cytochemical studies alone. The recognition of this subgroup is important for both practical and theoretical reasons. There are implications for treatment of the individual patient because treatment directed at a single lineage may not be effective. The two colour flow cytometry proved to be a useful tool for diagnosis and classification of acute leukaemia.
    Matched MeSH terms: Leukemia, Myeloid, Acute/classification; Leukemia, Myeloid, Acute/pathology*
  17. Goh BS, Tang CL, Tan GC
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 2):1023-1026.
    PMID: 31750119 DOI: 10.1007/s12070-015-0930-8
    Myeloid sarcoma is a rare malignant extramedullary neoplasm of myeloid precursor cells. This disorder may occur in concomitance with or precede development of acute or chronic myeloid leukemia. Sometimes, it is the initial manifestation of relapse in a previously treated acute myeloid leukemia. We report a case of 11 years old boy with acute myeloid leukemia in remission state, presented with short history of right otalgia associated with facial nerve palsy. Diagnosis of right acute mastoiditis with facial nerve palsy as complication of acute otitis media was made initially. Patient underwent simple cortical mastoidectomy but histopathology from soft tissue that was sent revealed diagnosis of myeloid sarcoma. A leukemic relapse was confirmed by paediatric oncologist through bone marrow biopsy. Chemotherapy was commenced but patient responded poorly to the treatment.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  18. Sutiman N, Nwe MS, Ni Lai EE, Lee DK, Chan MY, Eng-Juh Yeoh A, et al.
    Clin Lymphoma Myeloma Leuk, 2021 03;21(3):e290-e300.
    PMID: 33384264 DOI: 10.1016/j.clml.2020.11.016
    PURPOSE: To determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time.

    PATIENTS AND METHODS: Sixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia-Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients.

    RESULTS: Significant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014).

    CONCLUSION: Outcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.

    Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis; Leukemia, Myeloid, Acute/mortality*; Leukemia, Myeloid, Acute/therapy*
  19. Muda Z, Ibrahim H, Abdulrahman EJ, Menon BS, Zahari Z, Zaleha AM, et al.
    Med J Malaysia, 2008 Dec;63(5):415-6.
    PMID: 19803305 MyJurnal
    Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.
    Matched MeSH terms: Leukemia, Myeloid, Acute/microbiology*
  20. Raveendran S, Sarojam S, Vijay S, Prem S, Sreedharan H
    Malays J Med Sci, 2015 Sep;22(5):93-97.
    PMID: 28239274
    Acute myeloid leukaemia (AML) is one of the fatal haematological malignancies as a consequence of its genetic heterogeneity. At present, the prediction of the clinical response to treatment for AML is based not only on detection of cytogenetic aberrations but also by analysing certain molecular genetic alterations. There are limited in sights into the contribution, disease progression, treatment outcome, and characterisation with respect to the uncommon chromosomal abnormalities leading to AML. Here, we describe the clinical, morphological, cytogenetic, and mutational findings of a 52-year-old female patient with AML without maturation (AML-M1). Conventional karyotyping and spectral karyotyping (SKY) were done on metaphase chromosomes from bone marrow cells at the time of diagnosis. A mutation analysis was performed on the hotspot regions of various genes, including FLT3, CEBPA, NPM1, RAS, c-KIT, IDH1 and IDH2. Cytogenetic and mutation analyses revealed a novel translocation, t(X;2)(q28;p22), with both NPM1 and IDH1 mutations. To the best of our knowledge, the presence of both NPM1 and IDH1 mutations in t(X;2)(q28;p22) is a novel finding in AML.
    Matched MeSH terms: Leukemia, Myeloid, Acute
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