• Title/Summary/Keyword: Acute Leukemia

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Different Protein Expression between Human Eosinophilic Leukemia Cells, EoL-1 and Imatinib-resistant EoL-1 Cells, EoL-1-IR

  • Sung, Kee-Hyung;Kim, In-Sik;Lee, Ji-Sook
    • Biomedical Science Letters
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    • v.24 no.4
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    • pp.426-429
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    • 2018
  • Chronic eosinophilic leukemia (CEL) is characterized by eosinophilia and organ damage. Imatinib is widely used for treating CEL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Unfortunately, the cancer cells gain resistance against the drug after prolonged molecular-targeted therapies. Imatinib-resistant EoL-1 (EoL-1-IR) cells were produced from chronic eosinophilic leukemia cells (EoL-1) after treatment with imatinib for a long duration. Two-dimensional electrophoresis (2-DE) analysis revealed numerous protein variations in the EoL-1 and EoL-1-IR sub-types. Compared to the EoL-1 cells, expression levels of TIP49, RBBP7, α-enolase, adenosine deaminase, C protein, galactokinase, eukaryotic translation initiation factor, IFNγ, and human protein homologous to DROER were increased, whereas core I protein, proteasome subunit p42, heterogeneous ribonuclear particle protein, chain B, and nucleoside diphosphate were decreased in the EoL-1-IR cells. Taken together, these results contribute to understanding the pathogenic mechanism of drug-resistant diseases.

Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples

  • Barwe, Sonali P.;Gopalakrisnapillai, Anilkumar;Mahajan, Nitin;Druley, Todd E.;Kolb, E. Anders;Crowgey, Erin L.
    • Genomics & Informatics
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    • v.18 no.1
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    • pp.6.1-6.9
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    • 2020
  • Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

Lack of Association between Polymorphisms in Genes MTHFR and MDR1 with Risk of Childhood Acute Lymphoblastic Leukemia

  • Kreile, Madara;Rots, Dmitrijs;Piekuse, Linda;Cebura, Elizabete;Grutupa, Marika;Kovalova, Zhanna;Lace, Baiba
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9707-9711
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    • 2014
  • Background: Acute lymphoblastic leukemia (ALL) is a complex disease caused by interactions between hazardous exogenous or/and endogenous agents and many mild effect inherited susceptibility mutations. Some of them are known, but their functional roles still requireinvestigation. Age is a recognized risk factor; children with disease onset after the age of ten have worse prognosis, presumably also triggered by inherited factors. Materials and Methods: The MDR1 gene polymorphisms rs1045642, rs2032582 and MTHFR gene polymorphisms rs1801131 and rs1801133 were genotyped in 68 ALL patients in remission and 102 age and gender matched controls; parental DNA samples were also available for 42 probands. Results: No case control association was found between analyzed polymorphisms and a risk of childhood ALL development. Linkage disequilibrium was not observed in a family-based association study either. Only marginal association was observed between genetic marker rs2032582A and later disease onset (p=0.04). Conclusions: Our data suggest that late age of ALL onset could be triggered by mild effect common alleles.

67GaCitrate Scan in A Case of Granulocytic Sarcoma with Bone Marrow Remission of Acute Myelogenous Leukemia (관해된 급성 골수성 백혈병 환자에서 발생한 과립성 육종의 67Gacitrate Scan 소견)

  • Kim, Gwang-Weon;Chung, Byung-Cheon;Lee, Jae-Tae;Lee, Kyu-Bo;Whang, Kee-Suk
    • The Korean Journal of Nuclear Medicine
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    • v.24 no.2
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    • pp.337-342
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    • 1990
  • A case of a 39-year-old man with granulocytic sarcoma documented by positive Ga-67 scan is described and brief review of literature was performed. He was diagnosed as acute myelogenous leukemia and got complete remission with antileukemic chemotherapy for 7 months. On admission, picture of his bone marrow and peripheral blood showed remission state of leukemia. Radiologic examinations were performed for evaluation of lesions in head and chest, and findings of granulocytic sarcoma were suspected. So we got 67Gacitrate scan and pleural biopsy for identification of causes of intractable pleural effusion and skin lesion. Myeloblastomas (or granular sarcomas) proved by pleural biopsy were correctly identified by 67Gacitrate scan, and disease extent was clearly delineated. We believe that 67Gascintigraphy is very helpful in localizing and follow-up evaluation of granulocytic sarcoma.

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The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies

  • Yokota, Asumi;Huo, Li;Lan, Fengli;Wu, Jianqiang;Huang, Gang
    • Molecules and Cells
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    • v.43 no.2
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    • pp.145-152
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    • 2020
  • RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

Weight status in survivors of childhood acute lymphocytic leukemia in South Korea: a retrospective descriptive study

  • Yeongseon Kim;Kyung-Sook Bang
    • Child Health Nursing Research
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    • v.29 no.4
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    • pp.280-289
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    • 2023
  • Purpose: This study investigated weight status in survivors of childhood acute lymphocytic leukemia (ALL) and identified related factors. Methods: A retrospective review of the electronic medical records of survivors of childhood ALL (n=230) was conducted. We analyzed the survivors' characteristics, including sex, age, weight status at diagnosis, central nervous system involvement, risk classification, length of treatment, radiation therapy, and hematopoietic stem cell transplantation. Analysis of variance and the chi-squared test were applied to investigate influencing factors. Results: The weight status distribution was as follows: 23 individuals (10.0%) were classified as underweight, 151 individuals (65.7%) were healthy weight, and 56 individuals (24.3%) were overweight/obese. Age at diagnosis (F=10.03, p<.001), weight status at diagnosis (x2=43.41, p<.001), and risk classification (F=10.98, p=0.027) showed significant differences among the weight status groups. Survivors who were older at diagnosis and those in the very high-risk category had a higher likelihood of experiencing underweight status during their survivorship, while survivors who were overweight/obese at diagnosis were more likely to remain overweight/obese at the time of survival. Conclusion: Considering the potential health implications related to an unhealthy weight status in survivors of ALL, it is imperative to undertake early identification and implement interventions for at-risk individuals.

Growth and Differentiation Effects of Homer3 on a Leukemia Cell Line

  • Li, Zheng;Qiu, Hui-Ying;Jiao, Yang;Cen, Jian-Nong;Fu, Chun-Mei;Hu, Shao-Yan;Zhu, Ming-Qing;Wu, De-Pei;Qi, Xiao-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2525-2528
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    • 2013
  • The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by As2O3 through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

Surface Marker Analysis in Acute Leukemias (백혈병의 면역학적 표지자검사의 결과분석)

  • Moon, Jin-Young;Lee, Chae-Hoon;Kim, Kyung-Dong;Kim, Chung-Sook
    • Journal of Yeungnam Medical Science
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    • v.14 no.2
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    • pp.359-369
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    • 1997
  • We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.

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A Novel Translocation Involving RUNX1 and HOXA Gene Clusters in a Case of Acute Myeloid Leukemia with t(7;21)(p15;q22)

  • Moon, Yeonsook;Horsman, Douglas E.;Humphries, R. Keith;Park, Gyeongsin
    • IMMUNE NETWORK
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    • v.13 no.5
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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.

Anti-leukemic effects of JIPAESAN and its components on leukemic cells HL-60 (인간백혈병(人間白血病) 세포주(細胞株)에서 지패산(芷貝散)의 작용(作用)에 관(關)한 연구(硏究))

  • Hwang Kee-Myoung
    • Herbal Formula Science
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    • v.10 no.1
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    • pp.143-155
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    • 2002
  • In the hope of identifying anti-leukemic agents from traditional herbal medicines. this study was designed to investigate the anti-leukemic effects of the herbal medicine Jipaesan, which is composed of Angelica Dahurica and Fritillariae Verticillata. in acute promyeloid leukemia HL-60 cells. Jipaesan showed anti-proliferative effect through the induction of differentiation and apoptosis in HL -60 cells. Verticinone as a major differentiating agent and imperatorin as major apoptosis-inducing agent were isolated from the water extracts of F. Verticillata and A. Dahurica, respectively. Combined treatment of HL-60 cells with two major compounds showed synergy in the induction of differentiation. Since the induction of differentiation and/or apoptosis has therapeutic values in curing acute leukemic diseases. Jipaesan could be useful as an anti-leukemic agent.

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