• Title/Summary/Keyword: lymphoblastic leukemia

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Combined Study of Cytogenetics and Fluorescence in Situ Hybridization (FISH) Analysis in Childhood Acute Lymphoblastic Leukemia (ALL) in a Tertiary Cancer Centre in South India

  • Mazloumi, Seyed Hashem Mir;Madhumathi, D.S.;Appaji, L.;Prasannakumari, Prasannakumari
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3825-3827
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    • 2012
  • FISH is one of the most sensitive molecular methods to detect genetic abnormalities with DNA probes. When cytogenetic studies are normal or insufficient, FISH may detect cryptic rearrangements, rare or slowly proliferative abnormal populations in non-mitotic cells. We cytogenetically evaluated 70 childhood ALL - 67.1% were found to have an abnormal karyotype. The 23 patients (32.9%) with a normal karyotype were analyzed by FISH applying two probes; TEL/AML1 and MYB which detect cryptic rearrangements of t(12;21)(p13;q22) and deletion of (6q) respectively, associated with a good prognosis. Out of 23 patients, one was positive for t(12;21)(p13;q22) (4.3%). None of our patients were positive for MYB del(6q). Two patients showed an extra signal for MYB on chromosomes other than 6 (8.6 %) indicating amplification or duplication. Findings were compared with the available literature. Our study clearly indicated the integrated FISH screening method to increase the abnormality detection rate in a narrow range. FISH is less useful for diagnostic study of patients with suspected del(6q) but it helps in detecting known cryptic rearrangements as well as identification of new abnormalities(translocation , duplication and amplification) at the gene level.

Associations between AT-rich Interactive Domain 5B gene Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia: a Meta-analysis

  • Zeng, Hui;Wang, Xue-Bin;Cui, Ning-Hua;Nam, Seungyoon;Zeng, Tuo;Long, Xinghua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6211-6217
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    • 2014
  • Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL.

Effect of the Water Extract of Albizzia julibrissin on Cell Cycle Progression in the Human Leukemic Jurkat Cells (백혈병세포주 Jurkat의 세포주기 억제에 미치는 합환피(Albizzia julibrissin) 물 추출물의 효과)

  • Hwang, Sang-Gu;Lee, Hyung-Chul;Kim, Dae-Geun;An, Won-Gun;Jeon, Byung-Hun
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.29-34
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    • 2002
  • Albizzia julibrissin belonging to the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in Oriental traditional medicine. The water extract of A. julibrissin induced apoptosis in Jurkat T-acute lymphoblastic leukemia (ALL) cells as measured by cell morphology. The capability of this herb medicine to induce apoptosis was associated with proteolytic cleavage of specific target protein such as beta-catenin protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of A. julibrissin on cell cycle progression. Our results showed that GI checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

Effect of the Water Extract of Ajbizzia julibrissin on Apoptotic Cell Death in the Human Leukemic Jurkat T Cell Line (백혈병세포주 Jurkat T 세포에서 합환피 (Ajbizzia julibrissin) 물 추출물의 아포토시스 유도 효과)

  • 황상구;이형철;김춘관;김용익;주성민;김원신;전병훈
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.730-738
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    • 2001
  • Apoptosis is a morphologically and biochemically distinct form of cell death that occurs in many different cell types in a wide variety of organisms. Ajbizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract off julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability oft julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP-ribose) polymerase (PARP) protein suggesting the possible involvement of caspases. Our result skewed that Bcl-2 and Bax protein levels were not changed in all A julibrissin-treated groups compared to control group. These results suggest that A julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells.

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Serum Human Leukocyte Antigen-G and Soluble Interleukin 2 Receptor Levels in Acute Lymphoblastic Leukemic Pediatric Patients

  • Motawi, Tarek M.K.;Zakhary, Nadia I.;Salman, Tarek M.;Tadros, Samer A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5399-5403
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    • 2012
  • Aims and Background: Human leukocyte antigen-G and interleukin-2 receptor play pivotal roles in the proliferation of lymphocytes, and thus generation of immune responses. Their overexpression has been evidenced in different malignant hematopoietic diseases. This study aimed to validate serum soluble human leukocyte antigen-G (sHLA-G) and serum soluble interleukin-2 receptor (sIL-2R) as an additional tool for the diagnosis and follow up of acute lymphoblastic leukemia (ALL). Subjects and Methods: Both markers were determined by ELISA in the serum of 33 ALL pediatric patients before treatment and after intensification phase of chemotherapy as well as in the serum of 14 healthy donors that were selected as a control group. Results: ALL patients showed abnormal CBC and high serum lactate dehydrogenase, which were improved after chemotherapy. Also, there was a non-significant increase in serum sHLA-G in ALL patients compared with the control group. However, after chemotherapy, sHLA-G was increased significantly compared with before treatment. On the other hand, serum sIL-2R in ALL patients was increased significantly compared with the control group. After chemotherapy, sIL-2R decreased significantly compared with before treatment. Conclusions: From these results it could be suggested that measurement of serum sHLA-G might be helpful in diagnosis of ALL, while sIL-2R might be useful in diagnosis and follow-up of ALL in pediatric patients.

Comparison of Univariate and Multivariate Gene Set Analysis in Acute Lymphoblastic Leukemia

  • Soheila, Khodakarim;Hamid, AlaviMajd;Farid, Zayeri;Mostafa, Rezaei-Tavirani;Nasrin, Dehghan-Nayeri;Syyed-Mohammad, Tabatabaee;Vahide, Tajalli
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1629-1633
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    • 2013
  • Background: Gene set analysis (GSA) incorporates biological with statistical knowledge to identify gene sets which are differentially expressed that between two or more phenotypes. Materials and Methods: In this paper gene sets differentially expressed between acute lymphoblastic leukaemia (ALL) with BCR-ABL and those with no observed cytogenetic abnormalities were determined by GSA methods. The BCR-ABL is an abnormal gene found in some people with ALL. Results: The results of two GSAs showed that the Category test identified 30 gene sets differentially expressed between two phenotypes, while the Hotelling's $T^2$ could discover just 19 gene sets. On the other hand, assessment of common genes among significant gene sets showed that there were high agreement between the results of GSA and the findings of biologists. In addition, the performance of these methods was compared by simulated and ALL data. Conclusions: The results on simulated data indicated decrease in the type I error rate and increase the power in multivariate (Hotelling's $T^2$) test as increasing the correlation between gene pairs in contrast to the univariate (Category) test.

Clinical Significance of BCR-ABL Fusion Gene Subtypes in Chronic Myelogenous and Acute Lymphoblastic Leukemias

  • Ye, Yuan-Xin;Zhou, Juan;Zhou, Yan-Hong;Zhou, Yi;Song, Xing-Bo;Wang, Jun;Lin, Li;Ying, Bin-Wu;Lu, Xiao-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9961-9966
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    • 2014
  • Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.

20(S)-Ginsenoside Rh2 displays efficacy against T-cell acute lymphoblastic leukemia through the PI3K/Akt/mTOR signal pathway

  • Xia, Ting;Zhang, Jin;Zhou, Chuanxin;Li, Yu;Duan, Wenhui;Zhang, Bo;Wang, Min;Fang, Jianpei
    • Journal of Ginseng Research
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    • v.44 no.5
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    • pp.725-737
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    • 2020
  • Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

Informative Gene Selection Method in Tumor Classification

  • Lee, Hyosoo;Park, Jong Hoon
    • Genomics & Informatics
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    • v.2 no.1
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    • pp.19-29
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    • 2004
  • Gene expression profiles may offer more information than morphology and provide an alternative to morphology- based tumor classification systems. Informative gene selection is finding gene subsets that are able to discriminate between tumor types, and may have clear biological interpretation. Gene selection is a fundamental issue in gene expression based tumor classification. In this report, techniques for selecting informative genes are illustrated and supervised shaving introduced as a gene selection method in the place of a clustering algorithm. The supervised shaving method showed good performance in gene selection and classification, even though it is a clustering algorithm. Almost selected genes are related to leukemia disease. The expression profiles of 3051 genes were analyzed in 27 acute lymphoblastic leukemia and 11 myeloid leukemia samples. Through these examples, the supervised shaving method has been shown to produce biologically significant genes of more than $94\%$ accuracy of classification. In this report, SVM has also been shown to be a practicable method for gene expression-based classification.