• Title, Summary, Keyword: AML

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A Comparison of Gene Expression Profiles between Primary Human AML Cells and Therapy-related AML Cells

  • Kim, Young-Hun;Kim, Hyung-Soo;Hwang, Jun-Mo;Lee, Jin-Seok;Kim, Seong-Gon;Park, So-Young;Chang, Kyu-Tae;Kim, Kil-Soo;Ryoo, Zae-Young;Lee, Sang-Gyu
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.431-436
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    • 2008
  • To identify genes whose expression correlated with biological features of therapy-related AML (t-AML), we analyzed the expression profiles of de novo AML t(9;11) and t-AML t(9;11) bone marrow samples using previously published SAGE data. Three-hundred twenty-nine transcripts that satisfied statistical (P<0.05) and magnitude-of-change ($\geq$ 4-fold) criteria were identified as differentially expressed between de novo AML t(9;11) and t-AML t(9;11) cells. Of these transcripts, 301 (91%) matched known genes or ESTs and were classified according to functional categories (http://david.abcc.ncifcrf.gov/). The majority of differentially expressed genes in t-AML t(9;11) were involved in the regulation of biological and metabolic processes. Especially prominent among these were genes related to immune and drug responses. These results establish a framework for developing new drugs for the treatment of t-AML.

Overexpression of indoleamine 2,3-dioxygenase correlates with regulatory T cell phenotype in acute myeloid leukemia patients with normal karyotype

  • Arandi, Nargess;Ramzi, Mani;Safaei, Fatemeh;Monabati, Ahmad
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.294-298
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    • 2018
  • Background Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert $CD4^+CD25^-$ conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. Methods Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. Results Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). Conclusion Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

How to Establish Acute Myeloid Leukemia Xenograft Models Using Immunodeficient Mice

  • Shan, Wu-Lin;Ma, Xiao-Ling
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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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.

RUNX1 Mutations in the Leukemic Progression of Severe Congenital Neutropenia

  • Olofsen, Patricia A.;Touw, Ivo P.
    • Molecules and Cells
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    • v.43 no.2
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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).

Isolation and Characterization of Lactobacillus brevis AML15 Producing γ-Aminobutyric acid ((γ-Aminobutyric acid를 생산하는 Lactobacillus brevis AML15의 분리 및 특성)

  • Shin, Ji-Won;Kim, Dong-Geol;Lee, Yong-Woo;Lee, Hyoung-Seok;Shin, Kee-Sun;Choi, Chung-Sig;Kwon, Gi-Seok
    • Journal of Life Science
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    • v.17 no.7
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    • pp.970-975
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    • 2007
  • For the screening of ${\gamma}-aminobutyric$ acid (CABA)-producing bacteria, 86 bacterial strains which produce GABA were isolated from Kimchi and Salted fisk .Among these, three strains designated AML15, AML45-1, AML72 with relatively high GABA productivity were selecled by thin layer chromatography (TLC). To elucidate the relationship between isolated strains and the genus Lactobacillus, their 16S rDNA sequence were examined. The result of their DNA sequences showed 99% similarity with Lactobacillus brevis ATCC 367. On the basis of the these results, isolated strains were identified as Lactobacillus brevis and designated L. brevis AML15. In order to determine the optimum conditions for GABA production, the isolated strains were cultivated in pyridoxal phosphate (PLP) and monosodium glutami. acid (MSG). Results showed that L. brevis AML15 had the highest CABA productivity with 10,424 $nM/{\mu}l$ concentration in MRS broth containing 5% (w/v) MSG and 10 ${\mu}M$ PLP at pH 5.0. The results imply that L. brevis AML15 has the potential to be developed as a strain for GABA hyper-production.

FLT3-ITD Mutations in Acute Myeloid Leukemia Patients in Northeast Thailand

  • Kumsaen, Piyawan;Fucharoen, Goonnapa;Sirijerachai, Chittima;Chainansamit, Su-on;Wisanuyothin, Nittaya;Kuwatjanakul, Pichayanan;Wiangnon, Surapon
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4395-4399
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    • 2016
  • The FLT3-ITD mutation is one of the most frequent genetic abnormalities in acute myeloid leukemia (AML) where it is associated with a poor prognosis. The FLT3-ITD mutation could, therefore, be a potential molecular prognostic marker important for risk-stratified treatment options. We amplified the FLT3 gene at exon 14 and 15 in 52 AML patients (aged between 2 months and 74 years) from 4 referral centers (a university hospital and 3 regional hospitals in Northeast Thailand), using a simple PCR method. FLT3-ITD mutations were found in 10 patients (19.2%), being more common in adults than in children (21.1% vs. 14.3%) and more prevalent in patients with acute promyelocytic leukemia (AML-M3) than AML-non M3 (4 of 10 AML-M3 vs. 6 of 42 AML-non M3 patients). Duplication sequences varied in size-between 27 and 171 nucleotides (median=63.5) and in their location. FLT3-ITD mutations with common duplication sequences accounted for a significant percentage in AML patients in northeastern Thailand. This simple PCR method is feasible for routine laboratory practice and these data could help tailor use of the national protocol for AML.

Wild Carrot Oil Extract is Selectively Cytotoxic to Human Acute Myeloid Leukemia Cells

  • Tawil, Mirna;Bekdash, Amira;Mroueh, Mohammad;Daher, Costantine F.;Abi-Habib, Ralph J.
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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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.

Identification of a novel circularized transcript of the AML1 gene

  • Xu, Ai-Ning;Chen, Xiu-Hua;Tan, Yan-Hong;Qi, Xi-Ling;Xu, Zhi-Fang;Zhang, Lin-Lin;Ren, Fang-Gang;Bian, Si-Cheng;Chen, Yi;Wang, Hong-Wei
    • BMB Reports
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    • v.46 no.3
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    • pp.163-168
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    • 2013
  • The AML1 gene is an essential transcription factor regulating the differentiation of hematopoietic stem cells into mature blood cells. Though at least 12 different alternatively spliced AML1 mRNAs are generated, three splice variants (AML1a, AML1b and AML1c) have been characterized. Here, using the reverse transcription-polymerase chain reaction with outward-facing primers, we identified a novel non-polyadenylated transcript from the AML1 gene, with exons 5 and 6 scrambled. The novel transcript resisted RNase R digestion, indicating it is a circular RNA structure that may originate from products of mRNA alternative splicing. The expression of the novel transcript in different cells or cell lines of human and a number of other species matched those of the canonical transcripts. The discovery provides additional evidence that circular RNA could stably exist in vivo in human, and may also help to understand the mechanism of the regulation of the AML1 gene transcription.

Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region

  • Iqbal, Zafar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3541-3546
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    • 2014
  • TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia: A Retrospective Cohort Study in Makah Al Mukaramah, Saudi Arabia

  • Abdulateef, Nahla Ahmad Bahgat;Ismail, Manar Mohammad;Aljedani, Hanadi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.221-227
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    • 2014
  • Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.