• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7057-7063
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• 2013

The discovery of the immunodeficient mice has provided a tool for establishing animal models as hosts for in vivo analysis of AML. Various model systems have been established in the last few decades, and it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. In this review, we concentrate on the models of AML and discuss the development of immunodeficiency models for understanding of leukemogenesis, describe those now available and their values and document the methods used for establishing and identifying AML mice models, as well as factors influencing engraftment of human AML in immunodeficient mice. Thus, the function of this article is to provide clinicians and experimentalists with a chronological, comprehensive appraisal of all AML model systems.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.761-767
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• 2015

Background: In this study, we used Daucus carota oil extract (DCOE) to target acute myeloid leukemia (AML) cells. All the AML cell lines tested were sensitive to the extract while peripheral mononuclear cells were not. Analysis of mechanism of cell death showed an increase in cells positive for annexinV and for active caspases, indicating that DCOE induces apoptotic cell death in AML. Inhibition of the MAPK pathway decreased sensitivity of AML cells to DCOE, indicating that cytotoxicity may be dependent on its activity. In conclusion, DCOE induces selective apoptosis in AML cells, possibly through a MAPK-dependent mechanism.

• Genomics & Informatics
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• 제11권1호
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• pp.38-45
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• 2013

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.

• Molecules and Cells
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• 제46권10호
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Molecules and Cells
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• 제43권2호
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• pp.139-144
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• 2020

Somatic RUNX1 mutations are found in approximately 10% of patients with de novo acute myeloid leukemia (AML), but are more common in secondary forms of myelodysplastic syndrome (MDS) or AML. Particularly, this applies to MDS/AML developing from certain types of leukemia-prone inherited bone marrow failure syndromes. How these RUNX1 mutations contribute to the pathobiology of secondary MDS/AML is still unknown. This mini-review focusses on the role of RUNX1 mutations as the most common secondary leukemogenic hit in MDS/AML evolving from severe congenital neutropenia (SCN).

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5341-5344
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• 2013

Objectives: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). Methods: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. Results: From age group 10-19 years to age group ${\geq}60$ years, the percentage of LC decreased from $67.0{\pm}18.4%$ to $49.0{\pm}25.1%$ (F=2.353, P=0.041). LC percentage was higher in patients with balanced karyotypes ($65.7{\pm}22.4%$), than those with unbalanced karyotypes ($46.0{\pm}26.6%$) (u=3.444, P=0.001) or a normal karyotype ($49.9{\pm}22.1%$) (u=5.093, P<0.001). Patients with FLT3-ITD ($64.3{\pm}19.5%$) had higher LC percentages compared with those without ($54.2{\pm}24.3%$) (u=2.794, P=0.007). Conclusions: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.347-350
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• 2012

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.357-360
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• 2016

Background: Acute myeloid leukemia (AML) is an acquired clonal frequent malignant disorder of myeloid progenitor cells. Our aim was to study demographical and clinicopathological features of adult Pakistani AML patients at presentation. Materials and Methods: In this single centre study extending from January 2010 to December 2014, data were retrieved from the patient records with a predetermined performa and analyzed with SPSS version 22. Results: Overall 125 patients were diagnosed at our institution with de novo AML during the study period. There were 76 males and 49 females (ratio 1.5:1), with an age range between 15 and 85 years and a mean age of $38.8{\pm}20.1years$. The major complaints were fever (72.8%), generalized weakness (60%), bleeding (37.6%) and dyspnea (12%). Physical examination revealed pallor in 56.8%, splenomegaly and hepatomegaly in 16% and 12.8%, respectively, and lymphodenopathy in 10.4%. The mean hemoglobin was $8.19{\pm}2.12g/dl$ with a mean MCV of $86.0{\pm}9.83fl$, a mean total leukocyte count of $43.1{\pm}68.5{\times}10^9/l$, an ANC of $3.09{\pm}6.66{\times}10^9/l$ and a mean platelet count of $62.3{\pm}78.6{\times}10^9/l$. Conclusions: AML in Pakistani patients is seen in a relatively very young population with male preponderance, compared with the west. However, clinico-pathological features appear comparable to published data.

• IMMUNE NETWORK
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• 제13권5호
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• pp.222-226
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• 2013

Translocations involving chromosome 21q22 are frequently observed in hematologic malignancies including acute myeloid leukemia (AML), most of which have been known to be involved in malignant transformation through transcriptional dysregulation of Runt-related transcription factor 1 (RUNX1) target genes. Nineteen RUNX1 translocational partner genes, at least, have been identified, but not Homeobox A (HOXA) genes so far. We report a novel translocation of RUNX1 into the HOXA gene cluster in a 57-year-old female AML patient who had been diagnosed with myelofibrosis 39 months ahead. G-banding showed 46,XX,t(7;21)(p15;q22). The involvement of RUNX1 and HOXA genes was confirmed by fluorescence in situ hybridization.

• Journal of Yeungnam Medical Science
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• 제24권1호
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• pp.85-90
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• 2007

세계보건기구의 분류에 따르면 8번 염색체와 21번 염색체의 전위인 t(8;21)(q22;q22)를 가진 경우는 말초혈액이나 골수에 모세포가 20% 미만이더라도 급성골수성백혈병으로 분류하여야 하며, 이는 흔하지 않은 소견이다. 뿐만 아니라 이런 아형의 백혈병에서 골수의 저세포 충실도는 매두 드물다. 저자들은 골수세포충실도가 5% 미만으로 심하게 감소되어 있고, 골수의 모세포도 20% 미만인 환자에서 t(8;21)을 관찰하여 급성골수성백혈병으로 진단한 1례를 보고하는 바이다. 항암치료에 잘 반응하고 동종골수이식의 생착이 잘 이루어져, t(8;21)을 가진 일반적인 고세포충실성 급성골수성백혈병과 유사하게 좋은 예후를 가지는 것으로 생각된다.