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  1. Congenital papulonodular eruption: presenting sign of congenital leukaemia cutis
    Nanda A, El-Kamel MF, Al-Oneizi EM, Al-Ajmi M, Al-Enezi EM, Madda JP
    Clin Exp Dermatol, 2012 Jul;37(5):509-11.
    PMID: 22712859 DOI: 10.1111/j.1365-2230.2011.04270.x
    Congenital leukaemia (CL) is a rare malignancy that accounts for < 1% of cases of childhood leukaemias. Leukaemia cutis (LC) refers to cutaneous infiltration with leukaemic cells, and is seen in 30-50% of CL cases. It may precede, follow or occur simultaneously with leukaemia. If left untreated, the prognosis is usually poor, but early diagnosis and treatment may result in a favourable prognosis. We report a case of congenital leukaemia cutis with a progressive, violaceous papulonodular eruption (a 'blueberry muffin' rash), which had been noted at birth, as a presenting sign of acute myeloid leukaemia (AML), which on investigation was classified as AML, FAB M2 type with a t(8; 21)(p11;q22) chromosomal defect. The patient had a favourable response to AML chemotherapy.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  2. Hybrid acute leukaemia--a report of 3 cases
    Ng SC, Wong TK, Lin HP
    Ann Acad Med Singap, 1989 Nov;18(6):721-3.
    PMID: 2624424
    The simultaneous expression of both lymphoid and myeloid phenotypic features in acute leukaemia is rare. We report 3 cases of biphenotypic hybrid acute leukaemia seen in our institution. All 3 patients achieved remission with treatment for acute lymphoblastic leukaemia but two subsequently relapsed while on treatment. The hybrid acute leukaemias are important areas for further research both for delineation of basic biology and choice of optimal treatment.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology*
  3. Prognostic significance of morphological and cytochemical markers in adult acute myelogenous leukaemia: concepts and observations
    George E, Kamarulzaman E
    Med J Malaysia, 1979 Dec;34(2):184-6.
    PMID: 297198
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology*
  4. Unexpected infant death secondary to a pulmonary infiltration due to acute myelocytic leukaemia
    Ben Khelil M, Chkirbene Y, Mlika M, Haouet S, Hamdoun M
    Malays J Pathol, 2017 Aug;39(2):193-196.
    PMID: 28866704
    Acute myeloid leukaemia (AML) often presents with non-specific symptoms such as fatigue, anaemia or infection. Pulmonary involvement is uncommon in AML during the course of the disease and is usually caused by infection, haemorrhage, leukaemic pulmonary infiltrates and leukostasis. Lung localization of AML is very uncommon and potentially life threatening if not diagnosed and treated rapidly. The authors describe the sudden death of an asymptomatic five-month-infant because of a misdiagnosed lung localization of AML. Autopsy examination followed by histopathological studies showed an extensive leukostasis and extramedullary leukaemic infiltrating the lungs. Special stains and immunohistochemical studies revealed findings consistent with acute myelogenous leukaemia. This case suggests that underlying acute leukaemia should be considered as a cause of flu-like symptoms in infants. Medical personnel are urged to be alert to fever, sore throat, weakness and dyspnea that may be characteristic of serious systemic diseases.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology*
  5. Multiclass Benchmarking Framework for Automated Acute Leukaemia Detection and Classification Based on BWM and Group-VIKOR
    Alsalem MA, Zaidan AA, Zaidan BB, Albahri OS, Alamoodi AH, Albahri AS, et al.
    J Med Syst, 2019 Jun 01;43(7):212.
    PMID: 31154550 DOI: 10.1007/s10916-019-1338-x
    This paper aims to assist the administration departments of medical organisations in making the right decision on selecting a suitable multiclass classification model for acute leukaemia. In this paper, we proposed a framework that will aid these departments in evaluating, benchmarking and ranking available multiclass classification models for the selection of the best one. Medical organisations have continuously faced evaluation and benchmarking challenges in such endeavour, especially when no single model is superior. Moreover, the improper selection of multiclass classification for acute leukaemia model may be costly for medical organisations. For example, when a patient dies, one such organisation will be legally or financially sued for incidents in which the model fails to fulfil its desired outcome. With regard to evaluation and benchmarking, multiclass classification models are challenging processes due to multiple evaluation and conflicting criteria. This study structured a decision matrix (DM) based on the crossover of 2 groups of multi-evaluation criteria and 22 multiclass classification models. The matrix was then evaluated with datasets comprising 72 samples of acute leukaemia, which include 5327 gens. Subsequently, multi-criteria decision-making (MCDM) techniques are used in the benchmarking and ranking of multiclass classification models. The MCDM used techniques that include the integrated BWM and VIKOR. BWM has been applied for the weight calculations of evaluation criteria, whereas VIKOR has been used to benchmark and rank classification models. VIKOR has also been employed in two decision-making contexts: individual and group decision making and internal and external group aggregation. Results showed the following: (1) the integration of BWM and VIKOR is effective at solving the benchmarking/selection problems of multiclass classification models. (2) The ranks of classification models obtained from internal and external VIKOR group decision making were almost the same, and the best multiclass classification model based on the two was 'Bayes. Naive Byes Updateable' and the worst one was 'Trees.LMT'. (3) Among the scores of groups in the objective validation, significant differences were identified, which indicated that the ranking results of internal and external VIKOR group decision making were valid.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology*
  6. Biphenotypic hybrid acute leukaemia detected by two colour flow cytometry
    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/pathology*
  7. Nasal eschar: a warning sign of potentially fatal invasive fungal sinusitis in immunocompromised children
    Idris N, Lim LH
    J Pediatr Hematol Oncol, 2012 May;34(4):e134-6.
    PMID: 22430585 DOI: 10.1097/MPH.0b013e31824410e3
    Most invasive fungal sinusitis occurs in immunocompromised adult patients. We present the case study of a 12-year-old boy diagnosed with acute myeloblastic leukemia undergoing chemotherapy. He developed a progressive darkening discoloration over the dorsum of the nose that turned into an eschar. Nasal endoscopy revealed extensive necrotic tissue in the nasal cavity mucosa, inferior and middle turbinates, and septal cartilage that extended to the eschar of the skin over the nasal dorsum. Histopathology showed aspergillus invasive fungal rhinosinusitis.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  8. Fulltext Identification of FLT3 and NPM1 Mutations in Patients with Acute Myeloid Leukaemia
    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/pathology
  9. 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.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology*
  10. Fulltext Generation of dendritic cells from acute myeloid leukaemia cells and monocytes: our local experience
    Lim MN, Leong CF, Cheong SK, Seow HF
    Malays J Pathol, 2003 Dec;25(2):107-12.
    PMID: 16196366
    Dendritic cells (DC) are efficient and potent antigen-presenting cells. Pilot clinical trials indicated that DC loaded with tumour antigen could induce tumour-specific immune responses in various cancers including B-cell lymphoma, melanoma and prostate cancer. Owing to extensively low number of DC in the blood circulation, a variety of sources have been used to generate DC including monocytes, CD34+ stem cells and even with leukaemic blast cells. We demonstrate here a simple method to generate DC from acute myeloid leukaemia (AML) cells and monocytes from healthy donor or remission samples. AML cells or monocytes were cultured in RPMI 1640 media supplemented with foetal bovine serum or autologous serum where possible and different combinations of cytokines GM-CSF, IL-4 and TNF-alpha. The generated DC were evaluated for their morphology by phase contrast microscopy and May Grunwald Giemsa staining. Viability of cells was determined by trypan blue dye exclusion. Percentage of yields and immunophenotypes were carried out by flow cytometry. We found that cultured AML cells and monocytes developed morphological and immuno-phenotypic characteristics of DC. Monocytes are better than AML blast in generating DC and serve as a ready source for dendritic cell vaccine development.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  11. Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia
    Yunus NM, Johan MF, Ali Nagi Al-Jamal H, Husin A, Hussein AR, Hassan R
    Asian Pac J Cancer Prev, 2015;16(12):4869-72.
    PMID: 26163606
    BACKGROUND: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis.

    MATERIALS AND METHODS: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia.

    RESULTS: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374).

    CONCLUSIONS: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  12. Fulltext The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun
    Alhuthali HM, Bradshaw TD, Lim KH, Kam TS, Seedhouse CH
    BMC Cancer, 2020 Jul 07;20(1):629.
    PMID: 32635894 DOI: 10.1186/s12885-020-07119-2
    BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

    METHODS: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.

    RESULTS: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).

    CONCLUSIONS: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.

    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  13. Fulltext Molecular responses during chemotherapy in acute myeloid leukemias in predicting poor-response to standard chemotherapy
    Maha A, Cheong SK, Leong CF, Seow HF
    Malays J Pathol, 2009 Dec;31(2):81-91.
    PMID: 20514850 MyJurnal
    Signal transduction pathways are constitutively expressed in leukaemic cells resulting in aberrant survival of the cells. It is postulated that in cells of chemo-sensitive patients, chemotherapy induces apoptotic signals leading to cell death while survival signals are maintained in cells of chemo-resistant patients. There is very little information currently, on the expression of these mediators in patients immediately after chemotherapy initiation. We examined the expression pattern of proinflammatory cytokines, signaling molecules of the PI3K and MAPK pathways molecules and death receptor, DR5 on paired samples at diagnosis and during chemotherapy in acute myeloid leukaemia patients treated with cytosine arabinoside and daunorubicin. The results were correlated with remission status one month after chemotherapy. We found that in chemo-sensitive patients, chemotherapy significantly increased the percentage of cases expressing TNF-alpha (p = 0.025, n = 9) and IL-6 (p = 0.002, n = 11) compared to chemo-resistant cases. We also observed an increased percentage of chemo-sensitive cases expressing DR5 and phosphorylated p38, and Jnk. Thus, expression of TNF-alpha, IL-6, DR5, phospho-p38 and phospho-Jnk may regulate cell death in chemo-sensitive cases. In contrast, a significantly higher percentage of chemo-resistant cases expressed phospho-Bad (p = 0.027, n = 9). IL-beta and IL-18 were also found to be higher in chemo-resistant cases at diagnosis and during chemotherapy. Thus, expression of various cellular molecules in leukaemic blasts during chemotherapy may be useful in predicting treatment outcome. These cellular molecules may also be potential targets for alternative therapy.
    Matched MeSH terms: Leukemia, Myeloid, Acute/pathology
  14. Disruption of MAPK1 expression in the ERK signalling pathway and the RUNX1‑RUNX1T1 fusion gene attenuate the differentiation and proliferation and induces the growth arrest in t(8;21) leukaemia cells
    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/pathology
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