• 제목/요약/키워드: AML (M3)

검색결과 37건 처리시간 0.027초

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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    • 제17권9호
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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.

Associations of IL-10 Gene Polymorphisms with Acute Myeloid Leukemia in Hunan, China

  • Yao, Chen-Jiao;Du, Wei;Chen, Hai-Bing;Xiao, Sheng;Wang, Cheng-Hong;Fan, Zi-Li
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권4호
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    • pp.2439-2442
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    • 2013
  • We investigated the possible association of interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 patients and 137 healthy controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The IL-10 mRNA expression of AML patients and controls with different genotype was detected by real-time quantitative polymerase chain reaction (RT-PCR). Genetic analysis of IL-10 revealed that the -819AA genotype frequencies and the -819A allele frequencies in the AML group were higher than in the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in the AML group (75.6% vs 63.9%, P<0.05). IL-10 mRNA expression in incipient AML patients was obvious higher than the non-tumor group and the remission group ($7.78{\times}10^{-3}$ vs $2.43{\times}10^{-3}$, $3.64{\times}10^{-3}$, P<0.05).The study suggested that the haploid TA and genotype TA/TA may be associated with AML in Han people in Hunan province.The IL-10 SNPs at -819 and -592 sites were associated with AML and may affect IL-10 mRNA expression in AML patients.

Clinical Impact of Overexpression of FOXP3 and WT1 on Disease Outcome in Egyptian Acute Myeloid Leukemia Patients

  • Assem, Magda M;Osman, Ahmed;Kandeel, Eman Z;Elshimy, Reham AA;Nassar, Hanan R;Ali, Radwa E
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권10호
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    • pp.4699-4711
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    • 2016
  • Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

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

  • 신지원;김동걸;이용우;이형석;신기선;최충식;권기석
    • 생명과학회지
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    • 제17권7호통권87호
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    • pp.970-975
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    • 2007
  • 국내해안의 젓갈과 김치류로부터 86종의 GABA 생산균주를 분리하였다. 분리된 균주들을 Thin layer chromatography를 이용하여 GABA 생성능이 우수한 AML15, AML45-1, AML72의 3종의 균주를 선발하였다. 선별된 3종의 균주의 아미노산 분석 결과 GABA 생성능이 가장 우수한 AML15 균주를 본 실험에 사용하였다. AML15의 분류학적 위치를 규명하기 위하여 16S ribosomal DNA 영역의 부분염기서열 분석을 실시하였다. 165 rDNA 분석결과 Lactobacillus brevis ATCC 367과 99%의 유사도를 나타내어 L. brevis AML15로 명명하였다. MRS 배지에 최종 전환 농도로 설정된 5%(w/v) monosodium glutamic acid를 첨가하고 배지의 초기 pH를 4.0, 5.0과 6.0으로 조정하여 배양한 결과 배지의 초기 pH가 5.0일 때 GABA 생성능이 가장 높게 조사되었다. GABA 생산배지에 GAD 효소활성에 조효소로 작용하는 PLP를 0. 10. 50과 100 ${\mu}M$의 농도로 첨가하여 아미노산 분석결과 PLP를 10${\mu}M$ 첨가하였을 때 10,424 $nM/{\mu}$l의 GABA가생산되었다. PLP를 첨가하지 않았을 때보다 PLP 첨가 후 GABA 생성이 증가됨을 확인할 수 있었다.

Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells

  • Eun-Ji Choi;Bon-Kwan Koo;Eun-Hye Hur;Ju Hyun Moon;Ji Yun Kim;Han-Seung Park;Yunsuk Choi;Kyoo-Hyung Lee;Jung-Hee Lee;Eun Kyung Choi;Je-Hwan Lee
    • Biomolecules & Therapeutics
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    • 제31권3호
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    • pp.319-329
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    • 2023
  • Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Secretion and Expression of Matrix Metalloproteinase-2 and 9 from Bone Marrow Mononuclear Cells in Myelodysplastic Syndrome and Acute Myeloid Leukemia

  • Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Shanmukaiah, Chandrakala;Nadkarni, Anita H
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.1519-1529
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    • 2016
  • Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.

Acute Myeloid Leukemia: Clinical Spectrum of 125 Patients

  • Sultan, Sadia;Zaheer, Hasan Abbas;Irfan, Syed Mohammed;Ashar, Sana
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권1호
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    • pp.369-372
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    • 2016
  • Background: Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. Materials and Methods: This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. Results: A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). Conclusions: AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1).

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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    • 제46권3호
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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.

Prognostic Factors and Survival in Acute Myeloid Leukemia Cases: a Report from the Northeast of Iran

  • Allahyari, Abolghasem;Tajeri, Tarane;Sadeghi, Masoud
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.1547-1551
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    • 2016
  • Background: Acute myeloid leukemia (AML) is a clonal hematopoietic disorder resulting from genetic alterations in normal hematopoietic stem cells. The aim of this study was to evaluate prognostic factors and survival of AML patients in the Northeast of Iran. Materials and Methods: This retrospective study covered 96 patients with AML referred to Emam Reza Hospital, Mashhad city, Iran, from 2009 to 2015. Age, sex, blood group, type of AML, fever, consumption of amphotericin B, cytogenetic forms and survival were analyzed. Also, WBC, hemoglobin and platelet levels were checked. Mean follow-up was 30.5 months (60.4% mortality). Survival was plotted by GraphPad Prism 5 with Log-rank test. Results: The mean age for all AML patients at diagnosis was 40.4 years (range, 17-77 years). Some 42.7% patients were aged <35 years and 40.6% were male. In all patients, 76% had fever and 50% consumed amphotericin. T(15;17)(q22;q21) had the most prevalence (37.7%) compared to other forms. Out of 92 patients, O+(30.4%) was the most common blood group and AML-M5 (28.3%) the most common subtype. There was a significant difference in survival based on WBC and consumption of amphotericin B (P<0.05). Conclusions: WBC level, fever and consumption of amphotericin B proved to be factors for survival of AML patients. The mean age for patients in Iran is lower than other areas in the World and also survival in this study was higher than in other studies.

동백엽차와 화차의 세포독성 및 다제내성 극복효과 (Cytotoxicity and Chemosensitizing Effect of Camellia(Camellia japonica) Tea Extracts)

  • 황은주;차영주;박민희;이장원;이숙영
    • 한국식품영양과학회지
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    • 제33권3호
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    • pp.487-493
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    • 2004
  • 동백나무의 생엽과 생화, 그리고 이를 재료로 제다한 단일 동백엽차$.$화차 및 혼합 동백차의 세포독성과 다제 내성 극복을 규명하기 위하여, 4종의 인간암세포(MCF-7, Calu-5, SNU-601, AML-2/WT)와 1종의 다제내성 세포주(AML-2/ D100)를 이용하여 MTT방법으로 분석하였다. 동백의 어린엽 추출물은 Calu-6($IC_{50}$/: 79.8 $\mu\textrm{g}$/mL), SNU-601($IC_{50}$/: 39.0 $\mu\textrm{g}$/mL)에 대해 성엽과 꽃에 비해 세포독성 효과가 높았다. 단일 동백엽 차중, 찐차는 덜음차나 차차에 비해 상당한 생육 억제효과를 보였으며, 혼합 동백 차의 경우, Cahemix보다는 Catemix추출물이 MCF-7, Calu-6에 대한 $IC_{50}$/: 100 $\mu\textrm{g}$/mL 이하의 낮은 농도에서 세포 증식 억제 및 사멸 효과가 현저히 상승됨을 보여주었다. 특히 Catemix-2를 첨가하였을 때 MCF-7과 Calu-6 암세포에서 $IC_{50}$/값이 각각 75.3과 74.6으로 높은 억제효과를 나타내었다. 시료에 대하여 감수성 세포인 AML-2/WT에 대하여 세포독성을 측정하여 감수성 세포에 비하여 내성 세포에 대하여 선택적 세포독성 여부를 관찰한 결과, 대체적으로 $IC_{50}$/의 차이가 없거나 내성세포의 $IC_{50}$/이 높게 나타내어 그다지 선택적 세포독성을 나타내지 않는 것으로 보인다. 혼합 동백차의 경우, 내성세포에 대한 선택적 세포독성은 Catemix-2(녹차와 동백엽의 덜음차의 혼합)와 Catemix-3(녹차와 동백화차의 혼합)에서 0.9로 다소 효과를 보였으며, 내성 극복 효과는 Cahemix-1(CR: 1.7)에서 높게 관찰되었다.