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Mycobacterium abscessus Gastric Band Infection Complicated by Immune Reconstitution Inflammatory Syndrome and Cured in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

An N, Purtill D, Boan P

Open Forum Infect Dis, 2021 Feb;8(2):ofaa637.
PMID: 33553476 DOI: 10.1093/ofid/ofaa637

We present a case of abdominal gastric band-associated Mycobacterium abscessus infection, manifesting after the onset of acute myeloid leukemia, complicated by immune reconstitution inflammatory syndrome (IRIS), and cured while receiving an allogeneic hematopoietic stem cell transplant. IRIS should be considered in less classical situations where there is unexplained clinical deterioration.

Matched MeSH terms: Leukemia, Myeloid, Acute
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/genetics*; Leukemia, Myeloid, Acute/pathology
Fulltext Flexible model-based clustering of mixed binary and continuous data: application to genetic regulation and cancer

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
Fulltext Palm Raceme as a Promising Biomass Precursor for Activated Carbon to Promote Lipase Activity with the Aid of Eutectic Solvents

Abed KM, Hayyan A, Elgharbawy AAM, Hizaddin HF, Hashim MA, Hasan HA, et al.

Molecules, 2022 Dec 09;27(24).
PMID: 36557866 DOI: 10.3390/molecules27248734

This study concerns the role of activated carbon (AC) from palm raceme as a support material for the enhancement of lipase-catalyzed reactions in an aqueous solution, with deep eutectic solvent (DES) as a co-solvent. The effects of carbonization temperature, impregnation ratio, and carbonization time on lipase activity were studied. The activities of Amano lipase from Burkholderia cepacia (AML) and lipase from the porcine pancreas (PPL) were used to investigate the optimum conditions for AC preparation. The results showed that AC has more interaction with PPL and effectively provides greater enzymatic activity compared with AML. The optimum treatment conditions of AC samples that yield the highest enzymatic activity were 0.5 (NaOH (g)/palm raceme (g)), 150 min, and a carbonization temperature of 400 °C. DES was prepared from alanine/sodium hydroxide and used with AC for the further enhancement of enzymatic activity. Kinetic studies demonstrated that the activity of PPL was enhanced with the immobilization of AC in a DES medium.

Matched MeSH terms: Leukemia, Myeloid, Acute*
Fulltext Concomitant t(8;21) and trisomy 4 in a patient with acute myeloid leukemia (aml)

Phan, CL, Ong, TC, Chang, KM, Zubaidah, Z., Puteri Jamilatul, N.M.B.

Medicine & Health, 2010;5(1):45-48.
MyJurnal

The t(8;21)(q22;q22) is a frequently occurring aberration in acute myeloid leukemia (AML) (18-20%) and usually correlate with French-America-British (FAB) M2 subtype. Several studies showed that patients carrying this abnormality demonstrated good response to standard chemotherapy but also have a high incidence of disease relapse. Trisomy 4 is a rare and specific chromosomal abnormality occurring in AML M2 or M4 of the FAB subtypes. We report a case of a 33-year-old female with an apparently clinical and hematologic diagnosis of acute promyelocytic leukemia (APL) in whom cytogenetic analysis revealed an abnormal karyotype with trisomy 4, in addition to t(8;21). Trisomy 4 and t(8;21) in a patient with AML is rare. The significance of t(8;21) with trisomy 4 in AML are unclear but patients bearing this abnormality are associated with a poor prognosis.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext The Msi2 Protein expression positive correlation with favorable cytogenetics findings in AML

Nurasyikin, Y., Azma, R.Z., Suria, A.A., Chandramaya, S., Noraidah, M., Omayma, S.E.B

Medicine & Health, 2017;12(1):66-82.
MyJurnal

Acute myeloid leukaemia (AML) is the most common subtype of acute leukaemias with a poor outcome. Msi2 protein is a newly discovered prognostic marker and it has been considered as a new target for therapy in AML. The study of Msi2
protein expression in AML cases has not been performed in Malaysia, to date. The main aim of the present study was to observe the expression of Msi2 protein in AML patients by immunohistochemistry (IHC) and to correlate its expression
with the well-established prognostic and clinical parameters in AML as well as the overall survival (OS). Sixty four bone marrow trephine biopsy sections were immunostained for Msi2 protein. The percentage of blasts with positive reaction
and the intensity of the cytoplasmic and nuclear staining were evaluated. The expression of Msi2 protein was found in 95.3% cases with Msi2 pattern varying between the cases. In 71.9% of cases, the blasts showed total cellular positivity and 23.4% cases showed only cytoplasmic positivity. Majority showed high expression of Msi2 for cytoplasmic staining. Interestingly, there was significant correlation between total cellular staining and the intermediate cytogenetic subgroup (P=0.04). In conclusion, the results showed that the majority of the patients had high expression of Msi2 but this did not correlate to OS. However, the Msi2 expression correlated to the cytogenetic findings. The results suggest future extensive research to be conducted in order to ascertain the exact role of Msi2 positive blast cells in AML in our population and their association with prognosis and outcome.
Keywords: AML, cytogenetics, immunohistochemistry, Msi2 protein

Matched MeSH terms: Leukemia, Myeloid
Fulltext Survival of Children with Acute Leukaemia: A Single Centre Experience

Ariffin Nasir, Nor Fadhilah Zahari, Fahisham Taib, Norsarwany Mohamad

Malaysian Journal of Paediatrics and Child Health, 2020;26(1):4-13.
MyJurnal

Introduction: Acute leukaemia in children accounts for 25-30% of malignant diagnosis. Survival from acute leukaemia continue to improve. Treatment outcome depends on factors like gender, age at diagnosis, parental education, the initial total white cell count (TWC), cerebrospinal fluids (CSF) infiltration, immunophenotype and treatment response. Objectives: The objectives were to evaluate the survival of children with acute leukaemia who received chemotherapy and identify relevant factors. Methodology: The study was a retrospective record review at the Paediatric Oncology Unit, Hospital Universiti Sains Malaysia (Hospital USM). The data collected depending on pre-set research proforma from the year 1990 to 2010. Survival analysis of each type of leukaemia was completed using multiple Cox regression model. Results: A total of 334 cases were identified, only 283 patients received treatment at Hospital USM. There were 224 patients with acute lymphoblastic leukaemia (ALL) and 59 with acute myeloid leukaemia (AML). Overall survival (OS) rate at 3 months for ALL and AML were 89.3% and 72.9% respectively. The event-free survival (EFS) rate for ALL at 1, 3, and 5 years were 69.6%, 54.1% and 47.8% respectively. For AML, the EFS rate at 1, 3, and 5 years were 52.0%, 42.4% and 38.1% respectively. Multiple Cox regression model showed children’s age at diagnosis and early response to steroid therapy were the most significant prognostic factors for ALL survival, whereas the spleen size and treatment protocol were the most significant prognostic factors for AML. Conclusion: Survival rate in this study was comparable to developing countries. ALL had better outcome compared to AML.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Spectrum of hematological disorders in children diagnosed by bone marrow aspiration/biopsy: a retrospective study in a tertiary care center

Khan, Humayun Iqbal, Amir Rashid, Shabbir, A.S., Warriach, Israr B., Tariq, Rabia, Sarfraz, A., et al.

Malaysian Journal of Paediatrics and Child Health, 2011;17(1):0-0.
MyJurnal

Objective: This study assessed the pattern of clinical course of hematological disorders in children diagnosed by bone marrow aspiration/biopsy in a tertiary care centre. Setting: The study was conducted at the Department of Pediatrics, Lahore General Hospital, Pakistan. Design: A retrospective descriptive study. Duration of study: Jan 2006 to Dec 2010. Methods: The clinical and laboratory data of 250 patients including complete history, physical examination, investigations and bone marrow examination reports were collected and then analyzed retrospectively. On the basis of these data, relative frequency of different hematological disorders was determined. Results: A total of 250 patients were selected during this study period where their bone marrow was sent for the investigations. Out of these cases, double deficiency anemia was the commonest diagnosis (22%) followed by aplastic anemia (13.6%), megaloblastic anemia (13.2%) and iron deficiency anemia (5.6%). For hematological malignancies, acute lymphoblastic leukemia (ALL) was observed in 27 cases (10.8%) followed by acute myeloid leukemia (AML) in 12 cases (4.8%), lymphoma in 8 cases (3.2%) and chronic myeloid leukemia (CML) in only two cases. Idiopathic thrombocytopenic purpura (ITP) was reported as frequent as 13.2% (33 cases). Conclusion: The pattern of non malignant hematological disorders in children diagnosed by bone marrow aspiration/biopsy was more common than malignant conditions. Double deficiency anemia was the commonest non malignant condition followed by aplastic anemia, idiopathic thrombocytopenic purpura and megaloblastic anemia. ALL was the most common presentation of the hematological malignancy.

Matched MeSH terms: Leukemia, Myeloid, Acute
Systemic fusarium infection in cancer patients : a report of two cases

Mohamed, M., Ariffin, H., Arasu, A., Tuck Soon, S.H., Abdullah, W.A., Lin, H.P.

Malaysian Journal of Paediatrics and Child Health, 1998;10(2):55-58.
MyJurnal

Fusarium species is an emerging genus of fungal pathogens which until recently were rare causes of human disease apart from localized infection of the skin and nails. Two cases of fungaemia due to Fusarium sp. in children are described. The first child, an 8-year old girl with acute myeloid leukaemia developed character-sitic pyoderma gangrenosum-like skin lesions before succumbing to disseminated Fusarium infection and acute respiratory distress syndrome. The second child, a 5-month old boy, developed pneumonia associated with a transient erythematous skin rash while on chemother-apy for congenital leukaemia. Both patients had Fusarium isolated from blood. The second child improved after six weeks of treatment with ampho-tericin B and granulocyte-macrophage colony stimulat-ing factor but ultimately she died of the disease follow-ing discharge. Fusarium spp should be recognised as an opportunistic pathogen in immunocompromised patients. Current literature suggests that liposomal amphotericin B in conjunction with leukocyte growth factors are the treatment of choice in this potentially fatal infection.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Protein and gene expression of leukemia stem cells markers in acute myeloid leukemia

Amrina Mohamad Amin, Maha Abdullah, Sabariah Md Noor, Raudhawati Osman, Wan Hayati Mohd Yaacob, Cheong Soon Keng

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):23-23.
MyJurnal

Introduction: Acute myeloid leukaemia (AML) is a clonal haematological neoplasm characterised by proliferation of immature myeloid cells in the bone marrow resulting in impairment normal cell development in bone marrow. This leads to anaemia, thrombocytopenia and neutropenia. AML primarily affects older adults, with a median age at diagnosis of 69 years but is also seen in all other age groups. AML is recognized as a kind of cancer with marked heterogeneity in both biology of the cells and reactions to treatment. Treatment with intensive chemotherapy regi-mens of adult AML patients who are ≤ 60 years old results in hematologic remission in about 35% of patients, but at least 30% of these patients will experience a relapse. Mechanism leading to early relapse is still unclear. Leukaemia stem cell (LSC) is shown to correlate with poor prognosis. Biomarkers such as aldehyde dehydrogenase (ALDH) and CD34+CD38- have been identified as potential LSC biomarkers in previous studies. The objective of this study is to examine the expression of such markers for LSC and determine the association. Methods: Peripheral blood or bone marrow samples from untreated, newly diagnosed acute myeloid leukemias of all age, gender and race were collect-ed from Hospital Melaka and Kelang. Diagnosis of AML is based on WHO classification which include morphology, cytochemistry, immunophenotyping and cytogenetics. Mononuclear cells were isolated from bone marrow aspirate samples by gradient density centrifugation on Ficoll-Hypaque. Immunophenotyping using CD13, CD14, CD33, CD34, CD38 and ALDH were carried out to identify the presence and proportion of the various populations of inter-est. Results: There was a strong, positive correlation between ALDH and CD34+CD38- cell population, which was statistically significant (rs = 0.5989, p< 0.05). Conclusion: The strong correlation of ALDH activity and CD34+CD38- expression supported the potential of these biomarkers to identify LSCs cell in AML patients. However, due to the heterogeneity of AML, further studies using more markers and larger sample size are needed to determine the validity and to correlate with disease-free survival rate of AML patients.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Correlation between corresponding protein and MRNA in acute myeloid leukaemia (AML)

Siti Zuleha Idris, Stephnie Yiau Kang Xian, Lee CinDee, Eusni Rahayu Mohd. Tohit, Chang Kian Meng, Maha Abdullah

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):43-43.
MyJurnal

Introduction: Protein and gene expressions are intensively profiled for potential biomarkers in diagnosis or prognosis of diseases. The correlation between corresponding protein and mRNA of a gene is important to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. mRNA profiling is more commonly utilised as this method is cheaper and the technology more advanced. Acute myeloid leukaemia (AML) is a heterogeneous group of malignant precursors of the myeloid lineage that leads to death if not treated. Cytokines and death receptors are commonly evaluated in this disease in search of potential biomarkers; however, the mRNA/protein correlations of these biomarkers are still unclear. Methods: Semi-quantitative expression of mRNA expression and protein levels of IL-1β, IL-18Rα, IL-6, TNF-α and DR5 were measured by conventional polymerase reaction (PCR) and flow cytometry in 11 cases of AML at diagnosis. Correlation in the intensity of the PCR amplicon and corre-sponding mean fluorescence intensity of protein was determined by Spearman’s rank correlation test. Results: None of the cytokines/death receptor was significantly correlated except IL-6 (Rs= -0.6287, p=0.038). Unexpectedly, this was also a significant negative correlation. Conclusion: For the majority of selected biomarkers in AML, whether secreted or surface-expressed, mRNA and protein expressions were not significantly correlated. The strong negative correlation for IL-6 is worth further investigation.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Plasma and cell lysate proteins associated with treatment outcome in acute myeloid leukaemia

Fatemeh Barantalab, Pei-Pei Chong, Cindee Lee, Stephnie Kang Xian Yiau, Kian Meng Chang, Zainina Seman, et al.

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):23-29.
MyJurnal

Introduction: Drug-resistance is a major hindrance to successful treatment of AML. Current predictive biomarkers are mainly genetic aberrations and insufficient in foretelling treatment outcome in all acute myeloid leukaemia (AML) due to its heterogeneous and aggressive nature. Proteins are stable and reliable. Secreted proteins in AML may have predictive or prognostic values for early intervention. Proteomic studies on AML are few and further investigations will benefit in selection of best markers. The aim of the study was to identify differentially expressed plasma proteins in AML with different treatment outcome. Methods: Two-dimensional electrophoresis (2-DE) technique was utilised to identify proteins differentially expressed in chemo-sensitive/chemo-resistant AML. Plasma and peripheral blood mononuclear cell (PBMC) lysate proteome analysis were performed on six chemo-resistant, four chemo-sensitive and six healthy controls and seven chemo-resistant, three chemo-sensitive and six healthy controls, respectively. Each experiment was conducted in duplicate or triplicate. Images were captured and protein spots detected by software. Differentially expressed protein spots were excised from gel and proteins were identified using LC/MS/MS. Proteins spots that were also detected in healthy controls were excluded. Results: Comparing mean % volume of each spot demonstrated significantly enhanced expression of apoliprotein-E (APO-E) and haptoglobin (HP) (p

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Dose-and time-dependent suppression of Rac1 and STIM1 in acute myeloid leukaemia cell line model

Eman S. Algariri, Rabiatul Basria S.M.N. Mydin, Emmanuel Jairaj Moses, Simon Imakwu Okekpa, Nur Arzuar Abdul Rahim, Narazah Mohd Yusoff

Malaysian Journal of Medicine and Health Sciences, 2020;16(3):238-242.
MyJurnal

Introduction: Rac1 and STIM1 genes are emerging therapeutic targets for cancers. However, their roles in acute my- eloid leukaemia (AML) are not well understood. The goal of this study was to evaluate the effects of dose and time on Rac1 and STIM1 knockdown in the AML cell line model (THP-1 cells). Methods: THP-1 cells were transfected with siRac1 at doses of 50, 100, and 200 nM or dsiSTIM1 at doses of 2, 5, and 10 nM. Expression level of Rac1 and STIM1 then were assessed at time points between 12 and 72 h post-transfection using real-time reverse transcription poly- merase chain reaction. Results: Compared to the control, 87% Rac1 knockdown was attained with 50 nM siRac1 at 24 h post-transfection, and 70% STIM1 knockdown was achieved with 10 nM dsiSTIM1 at 48 h post-transfection. Conclusion: These results show that effective knockdown of Rac1 and STIM1 is possible, and therapy that includes Rac1 and STIM1 inhibitors eventually could provide a new and highly effective strategy for AML treatment.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Depression and quality of life among patients with hematological cancer in a Malaysian hospital

Priscilla, D., Hamidin, A., Azhar, M. Z., Noorjan, K. O. N., Salmiah, M. S., Bahariah, K.

Malaysian Journal of Medicine and Health Sciences, 2011;7(1):65-74.
MyJurnal

Objective: To determine the prevalence of major depressive disorder (MDD) in hematological cancer patients and to investigate MDD with quality of life. Methods: The research, which uses a cross sectional design, has been carried out at Ampang Hospital, Kuala Lumpur. The hospital is a tertiary referral center for cancer cases that include non-Hodgkin lymphoma, acute myelogenous leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma and other hematological cancers. In total, 105 patients with hematological malignancies were included in the study. This study employed the MINI International Neuropsychiatric Interview for diagnosis of MDD, the Patient Health Questionnaire (PHQ-9) for symptom severity of depression and the European Organisation for Research and Treatment of Cancer Quality Of Life questionnaire (EORTC QLQ-C30) to assess the quality of life of the respondents. Result: The response rate was 83.3%. The prevalence of MDD was 24.8% (n=26) with the majority of cases classified as moderately severe depression (38.5%). About 92.3% (n=24) of depressed hematological cancer patients were diagnosed with a current episode of MDD. The depressed patients also had significantly reduced quality of life in physical, role, emotional, cognitive and social domains (p

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Differential expression patterns of leukaemia associated genes in leukaemia cell lines compared to healthy controls

Ang Pei-Shen, Rajesh Ramasamy, Noor Hamidah Hussin, Cheong Soon-Keng, Seow Heng-Fong, Maha Abdullah

Malaysian Journal of Medicine and Health Sciences, 2016;12(1):0-0.
MyJurnal

Introduction: The phenotype and genotype of cancer cells portray hallmarks of cancer which may
have clinical value. Cancer cell lines are ideal models to study and confirm these characteristics. We
previously established two subtracted cDNA libraries with differentially expressed genes from an
acute myeloid leukaemia patient with poor prognosis (PP) and good prognosis (GP). Objective: To
compare gene expression of the leukaemia associated genes with selected biological characteristics
in leukaemia cell lines and normal controls. Methodology: Expression of 28 PP genes associated
with early fetal/embryonic development, HOX-related genes, hematopoiesis and aerobic glycolysis/
hypoxia genes and 36 GP genes involved in oxidative phosphorylation, protein synthesis, chromatin
remodelling and cell motility were examined in B-lymphoid (BV173, Reh and RS4;11) and myeloid
(HL-60, K562) leukaemia cell lines after 72h in culture as well as peripheral blood mononuclear cells
from healthy controls (N=5) using semi-quantitative polymerase chain reaction (PCR) method. Cell
cycle profiles were analysed on flow cytometry while MTT cytotoxicity assay was used to determine
drug resistance to epirubicin. Results: Genes expressed significantly higher in B-lymphoid leukaemia
cell lines compared to healthy controls were mostly of the GP library i.e. oxidative phosphorylation
(3/10), protein synthesis (4/11), chromatin remodelling (3/3) and actin cytoskeleton genes (1/5). Only
two genes with significant difference were from the PP library. Cancer associated genes, HSPA9 and
PSPH (GP library) and BCAP31 (PP library) were significantly higher in the B-lymphoid leukemia cell
lines. No significant difference was observed between myeloid cell lines and healthy controls. This
may also be due heterogeneity of cell lines studied. PBMC from healthy controls were not in cell cycle.
G2/M profiles and growth curves showed B-lymphoid cells just reaching plateau after 72 hour culture
while myeloid cells were declining. IC50 values from cytotoxicity assay revealed myeloid cell lines had
an average 13-fold higher drug resistance to epirubicin compared to B-lymphoid cell lines. Only CCL1,
was expressed at least two-fold higher in myeloid compared to B-lymphoid cell lines. In contrast,
MTRNR2, EEF1A1, PTMA, HLA-DR, C6orf115, PBX3, ENPP4, SELL, and IL3Ra were expressed
more than 2-fold higher in B-lymphoid compared to myeloid cell lines studied here. Conclusion: Thus,
B-lymphoid leukaemia cell lines here exhibited active, proliferating characteristics closer to GP genes.
Higher expression of several genes in B-lymphoid compared to myeloid leukaemia cell lines may be
useful markers to study biological differences including drug resistance between lineages.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Microarray-Based Genomic Analysis Identifies Germline and Somatic Copy Number Variants and Loss of Heterozygosity in Acute Myeloid Leukaemia

Ambayya, Angeli, Sasmita, Andrew Octavian, Zainina Seman, Chang, Kian Meng, Sathar, Jameela, Yegappan, Subramanian, et al.

Malaysian Journal of Medicine and Health Sciences, 2018;14(103):1-14.
MyJurnal

Insights into molecular karyotyping using comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. The applicability of a customised CGH+SNP 180K DNA microarray in the diagnostic evaluation of Acute Myeloid Leukaemia (AML) in comparison with conventional karyotyping was assessed in this study. Methods: Paired tumour and germline post induction (remission sample obtained from the same patient after induction) DNA were used to delineate germline variants in 41 AML samples and compared with the karyotype findings. Results: After comparing the tumour versus germline DNA, a total of 55 imbalances (n 5-10 MB = 21, n 10-20 MB = 8 and n >20 MB = 26) were identified. Gains were most common in chromosome 4 (26.7%) whereas losses were most frequent in chromosome 7 (28.6%) and X (25.0%). CN-LOH was mostly seen in chromosome 4 (75.0%). Comparison between array CGH+SNP and karyotyping revealed 20 cases were in excellent agreement and 13 cases did not concord whereas in 15 cases finding could not be confirmed as no karyotypes available. Conclusion: The use of a combined array CGH+SNP in this study enabled the detection of somatic and germline CNVs and CN-LOHs in AML. Array CGH+SNP accurately determined chromosomal breakpoints compared to conventional cytogenetics in relation to presence of CNVs and CN-LOHs.

Matched MeSH terms: Leukemia, Myeloid, Acute
Physical activity of pediatric patients with acute leukemia undergoing induction or consolidation chemotherapy

Tan SY, Poh BK, Chong HX, Ismail MN, Rahman J, Zarina AL, et al.

Leuk. Res., 2013 Jan;37(1):14-20.
PMID: 23099236 DOI: 10.1016/j.leukres.2012.09.005

This study aimed to assess the physical activity levels of pediatric patients with acute leukemia undergoing chemotherapy. Thirty-eight pediatric patients and matched controls, aged 3-12 years old, were measured for weight, height, and other anthropometric parameters. Physical activity was assessed using actical accelerometer and activity log book. Patients recorded significantly lower mean total activity counts (26.2±30.2 cpm vs. 192.2±68.8 cpm; p<0.01) and spent more time in sedentary activities (1301±121 min vs. 1020±101 min; p<0.001) compared to controls. They also achieved fewer 1-5-min bouts of moderate-vigorous physical activity (MVPA) compared to controls (1.50±5.95 vs. 37.38±40.36; p<0.001). In conclusion, patients had lower physical activity level and intensity; and simple exercise intervention programs may be needed to minimize the detrimental effects of prolonged sedentary behaviors.

Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy; Leukemia, Myeloid, Acute/physiopathology*
AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-β response in infected mammalian cells

Gaur P, Kumar P, Sharma A, Lal SK

Lett Appl Microbiol, 2020 Apr;70(4):252-258.
PMID: 31990997 DOI: 10.1111/lam.13279

Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-β levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-β levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-β. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-β response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Prevalence of Vitamin B12 Deficiency and its Associated Factors among Patients with Type 2 Diabetes Mellitus on Metformin from a District in Malaysia

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
Potential CD34 signaling through phosphorylated-BAD in chemotherapy-resistant acute myeloid leukemia

Yiau SK, Lee C, Mohd Tohit ER, Chang KM, Abdullah M

J Recept Signal Transduct Res, 2019 Jun;39(3):276-282.
PMID: 31509041 DOI: 10.1080/10799893.2019.1660899

Acute myeloid leukemia (AML) constitutively express growth factors and cytokines for survival. Chemotherapy alters these signals to induce cell death. However, drug resistance in AML remains a major hindrance to successful treatment and early warning is unavailable. Modulation of signaling pathways during chemotherapy may provide a window to detect response and predict treatment outcome. Blood samples collected from AML patients before and at day-3 of induction therapy were compared for changes in expression of CD117, CD34, pro-inflammatory cytokines and mediators of Akt and MAPK pathways, using multi-color flow cytometry. Nine patients were diagnosed as drug-resistant and seven sensitive to chemotherapy. Twelve were paired. Average percentages of CD34 (66.8 ± 11.7% vs. 26.2 ± 5.8%, p = 0.033) and pBAD (66.9 ± 8.2% vs. 28.9 ± 8.2%, p = 0.016) were significantly increased in chemo-resistant (N = 9) compared to chemo-sensitive (N = 5) samples. Percentages of CD34 were strongly correlated with pBAD (R = 0.785; p = 0.001; N = 14) and pFKHR (R = 0.755; p = 0.002; N = 14) at day-3 induction. Chemo-sensitive cases expressed significantly higher percentages of IL-18Rα (71.9 ± 9.6% vs. 29.8 ± 5.8%, p = 0.016). Though not significantly different in the outcome, IL-1β was strongly associated with activated Akt-S473, IL-6 with phosphorylated JNK and FKHR while TNF-α appeared to trigger Bim, in treated samples. These preliminary results suggested AML cells resistant to chemotherapy increased expression of CD34 and may signal through pBAD while cells sensitive to chemotherapy-induced IL18Rα expression. These were observed early during induction therapy. Identifying CD34 is interesting as it is a convenient marker to monitor drug-resistance in AML patients. Inhibition of CD34 and pBAD signaling may be important in treating drug-resistant AML.

Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/metabolism*

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