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Leukemia, lymphoma, genomics, genes, hematology

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https://www.readbyqxmd.com/read/27690235/dnmt3a-is-a-haploinsufficient-tumor-suppressor-in-cd8-peripheral-t-cell-lymphoma
#1
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27639374/comprehensive-genomic-characterization-of-five-canine-lymphoid-tumor-cell-lines
#2
Sarah C Roode, Daniel Rotroff, Kristy L Richards, Peter Moore, Alison Motsinger-Reif, Yasuhiko Okamura, Takuya Mizuno, Hajime Tsujimoto, Steven E Suter, Matthew Breen
BACKGROUND: Leukemia/lymphoma cell lines have been critical in the investigation of the pathogenesis and therapy of hematological malignancies. While human LL cell lines have generally been found to recapitulate the primary tumors from which they were derived, appropriate characterization including cytogenetic and transcriptional assessment is crucial for assessing their clinical predictive value. RESULTS: In the following study, five canine LL cell lines, CLBL-1, Ema, TL-1 (Nody-1), UL-1, and 3132, were characterized using extensive immunophenotyping, karyotypic analysis, oligonucleotide array comparative genomic hybridization (oaCGH), and gene expression profiling...
2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27619989/mutational-analysis-of-tp53-gene-in-tunisian-familial-hematological-malignancies-and-sporadic-acute-leukemia-cases
#3
Walid Sabri Hamadou, Sawsen Besbes, Violaine Bourdon, Yosra Ben Youssef, Mohamed Adnène Laatiri, Testsuro Noguchi, Abderrahim Khélif, Hagay Sobol, Zohra Soua
Mutations are responsible for familial cancer syndromes which account for approximately 5-10 % of all types of cancers. Familial cancers are often caused by genetic alterations occurring either in tumor suppressor or genomic stability genes such as TP53. In this study, we have analyzed the TP53 gene by direct sequencing approach, in a panel of 18 Tunisian familial hematological malignancies cases including several forms of leukemia, lymphoma and myeloid syndrome and 22 cases of sporadic acute leukemia. In one familial case diagnosed with acute lymphoblastic leukemia, we reported an intronic substitution 559+1 G>A which may disrupt the splice site and impact the normal protein function...
September 12, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27491640/enhanced-car-t-cell-engineering-using-non-viral-sleeping-beauty-transposition-from-minicircle-vectors
#4
R Monjezi, C Miskey, T Gogishvili, M Schleef, M Schmeer, H Einsele, Z Ivics, M Hudecek
Immunotherapy with T cell modified with gamma-retroviral or lentiviral (LV) vectors to express a chimeric antigen receptor (CAR) has shown remarkable efficacy in clinical trials. However, the potential for insertional mutagenesis and genotoxicity of viral vectors is a safety concern, and their cost and regulatory demands a roadblock for rapid and broad clinical translation. Here, we demonstrate that CAR T cells can be engineered through non-viral Sleeping Beauty (SB) transposition of CAR genes from minimalistic DNA vectors called minicircles (MCs)...
August 5, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27134162/promoter-hypomethylation-and-expression-is-conserved-in-mouse-chronic-lymphocytic-leukemia-induced-by-decreased-or-inactivated-dnmt3a
#5
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Abhinav Suresh, Samuel J Pirruccello, Vipul Shukla, Runqing Lu, Stefan Costinean, Angie Rizzino, Adam R Karpf, Shantaram Joshi, Patrick Swanson, Rene Opavsky
DNA methyltransferase 3a (DNMT3A) catalyzes the formation of 5-methyl-cytosine in mammalian genomic DNA, and it is frequently mutated in human hematologic malignancies. Bi-allelic loss of Dnmt3a in mice results in leukemia and lymphoma, including chronic lymphocytic leukemia (CLL). Here, we investigate whether mono-allelic loss of Dnmt3a is sufficient to induce disease. We show that, by 16 months of age, 65% of Dnmt3a(+/-) mice develop a CLL-like disease, and 15% of mice develop non-malignant myeloproliferation...
May 10, 2016: Cell Reports
https://www.readbyqxmd.com/read/26877874/recq-helicases-are-deregulated-in-hematological-malignancies-in-association-with-a-prognostic-value
#6
Elena Viziteu, Alboukadel Kassambara, Philippe Pasero, Bernard Klein, Jerome Moreaux
BACKGROUND: RECQ helicase family members act as guardians of the genome to assure proper DNA metabolism in response to genotoxic stress. Hematological malignancies are characterized by genomic instability that is possibly related to underlying defects in DNA repair of genomic stability maintenance. METHODS: We have investigated the expression of RECQ helicases in different hematological malignancies and in their normal counterparts using publicly available gene expression data...
2016: Biomarker Research
https://www.readbyqxmd.com/read/26458445/-recent-advancements-in-molecular-cytogenetics-for-hematological-malignancies-identification-of-novel-pvt1-fusion-genes
#7
Masafumi Taniwaki
Specific chromosomal abnormalities are of diagnostic and prognostic relevance as well as providing clues for the identification of causative genes in patients with hematological malignancies. Genomic array (GA) is a powerful tool for identifying both microdeletion and precise DNA breakpoints in the genes of interest. For example, GA was able to detect CDKN2A and CDKN2B deletions in a small region only 69kb in size at 9p21 that were frequently found in patients with double-hit lymphoma. Using GA combined with spectral karyotyping, fluorescence in situ hybridization, and RT-PCR, we have identified a novel PVT1 rearrangement at 8q24 which were partnered with NBEA and WWOX in multiple myeloma (MM)...
October 2015: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/26458435/-genetics-of-hereditary-hematological-malignancies
#8
Masatoshi Takagi
Familial predisposition to hematological malignancies has been recognized. Some of these malignancies are part of a well-characterized familial cancer predisposition syndrome, while others are independent of cancer predisposition, and demonstrate unique familial leukemia/lymphoma syndromes. Primary immunodeficiency is also strongly associated with the development of lymphoid malignancy. Primary immunodeficiency and leukemia/lymphoma are based on the same concept, which involves differentiation blockage. Bone marrow failure syndrome is also known to be associated with susceptibility to hematological malignancy development...
October 2015: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/26301057/prevalence-of-human-t-lymphotropic-virus-types-i-and-ii-in-patients-with-hematological-disorders-in-isfahan-iran
#9
Mohammadreza Mahzounieh, Mohammadreza Ghorani, Ali Karimi, Batoul Pourgheysari, Razieh Nikoozad
BACKGROUND: Human T-cell lymphotropic virus types Ι and ΙΙ (HTLV-Ι and HTLV-II) are deltaretroviruses which may cause leukemia, lymphoma and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition, HTLV-1 may be related to thalassemia and hemophilia cases after blood transfusion. OBJECTIVES: The aim of this study was evaluation of the prevalence of HTLVs in patients with hematological disorders (leukemia, thalassemia, lymphoma and hemophilia)...
June 2015: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/26116531/niclosamide-an-anti-helminthic-molecule-downregulates-the-retroviral-oncoprotein-tax-and-pro-survival-bcl-2-proteins-in-htlv-1-transformed-t-lymphocytes
#10
Di Xiang, Yunsheng Yuan, Li Chen, Xin Liu, Chandra Belani, Hua Cheng
Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis...
August 14, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25843568/molecular-studies-reveal-a-mll-mllt3-gene-fusion-displaced-in-a-case-of-childhood-acute-lymphoblastic-leukemia-with-complex-karyotype
#11
Daniela Ribeiro Ney Garcia, Thomas Liehr, Mariana Emerenciano, Claus Meyer, Rolf Marschalek, Maria do Socorro Pombo-de-Oliveira, Raul C Ribeiro, Marcelo Gerardin Poirot Land, Maria Luiza Macedo Silva
Rearrangement of the mixed lineage-leukemia gene (MLL-r) is common in hematological diseases and is generally associated with poor prognosis. The mixed-lineage leukemia gene translocated to, 3 (MLLT3) gene (9p22) is a frequent MLL-r partner (∼18% of leukemias with MLL rearrangement) and is characterized by the translocation t(9;11) (p22;q23), forming an MLL-MLLT3 gene fusion. MLL-r are usually simple reciprocal translocations between two different chromosomes, although karyotypes with complex MLL-r have been observed...
April 2015: Cancer Genetics
https://www.readbyqxmd.com/read/25748621/genes-and-childhood-leukemia
#12
REVIEW
Julita Kęsy, Danuta Januszkiewicz-Lewandowska
Leukemia is a heterogeneous hematologic malignancy originating from a multipotent hematopoietic stem cell. It ranks among the commonest cancers in childhood and is characterized by excessive proliferation and differentiation block. The process of leukemogenesis is governed by genetic changes at both the cytogenetic and molecular level. According to numerous analyses, a large spectrum of mutations and rearrangements underlying the disease affect essential cellular transduction pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators...
2015: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/25644173/genome-wide-analyses-identify-klf4-as-an-important-negative-regulator-in-t-cell-acute-lymphoblastic-leukemia-through-directly-inhibiting-t-cell-associated-genes
#13
Wei Li, Zhiwu Jiang, Tianzhong Li, Xinru Wei, Yi Zheng, Donghai Wu, Lijian Yang, Shaohua Chen, Bing Xu, Mei Zhong, Jue Jiang, Yufeng Hu, Hexiu Su, Minjie Zhang, Xiaojun Huang, Suxia Geng, Jianyu Weng, Xin Du, Pentao Liu, Yangqiu Li, Hudan Liu, Yao Yao, Peng Li
BACKGROUND: Kruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood. METHODS: Inducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo...
2015: Molecular Cancer
https://www.readbyqxmd.com/read/25326804/age-related-mutations-associated-with-clonal-hematopoietic-expansion-and-malignancies
#14
Mingchao Xie, Charles Lu, Jiayin Wang, Michael D McLellan, Kimberly J Johnson, Michael C Wendl, Joshua F McMichael, Heather K Schmidt, Venkata Yellapantula, Christopher A Miller, Bradley A Ozenberger, John S Welch, Daniel C Link, Matthew J Walter, Elaine R Mardis, John F Dipersio, Feng Chen, Richard K Wilson, Timothy J Ley, Li Ding
Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age...
December 2014: Nature Medicine
https://www.readbyqxmd.com/read/24968698/genomic-characterization-of-acute-leukemias
#15
REVIEW
Sabina Chiaretti, Valentina Gianfelici, Giulia Ceglie, Robin Foà
Over the past two decades, hematologic malignancies have been extensively evaluated due to the introduction of powerful technologies, such as conventional karyotyping, FISH analysis, gene and microRNA expression profiling, array comparative genomic hybridization and SNP arrays, and next-generation sequencing (including whole-exome sequencing and RNA-seq). These analyses have allowed for the refinement of the mechanisms underlying the leukemic transformation in several oncohematologic disorders and, more importantly, they have permitted the definition of novel prognostic algorithms aimed at stratifying patients at the onset of disease and, consequently, treating them in the most appropriate manner...
2014: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/24786297/the-epigenetic-landscape-of-t-cell-acute-lymphoblastic-leukemia
#16
REVIEW
Joni Van der Meulen, Nadine Van Roy, Pieter Van Vlierberghe, Frank Speleman
The genetic landscape of T-ALL has been very actively explored during the past decades. This leads to an overwhelming body of exciting novel findings providing insight into (1) the genetic heterogeneity of the disease with marked genetic subsets, (2) the mechanisms by which aberrant T-cell development drive leukemogenesis and (3) emerging opportunities for novel therapeutic interventions. Of further interest, recent genome wide sequencing studies identified proteins that actively participate in the regulation of the T-cell epigenome as novel oncogenes and tumor suppressor genes in T-ALL...
August 2014: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/24781345/exploring-the-association-of-succinate-dehydrogenase-complex-mutations-with-lymphoid-malignancies
#17
R Renella, J Carnevale, K A Schneider, J L Hornick, H Q Rana, K A Janeway
The succinate dehydrogenase (SDH) complex exerts a fundamental role in mitochondrial cellular respiration and mutations in its encoding genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHx) lead to a number of inherited endocrine cancer predisposition syndromes, including familial paraganglioma/pheochromocytoma. Recent studies suggest a possible role for the SDH complex and other mitochondrial enzymes in the pathogenesis of hematological malignancy. Our aim was to search and identify pedigrees of patients affected by germline SHDx mutations treated at our institution for endocrine and other tumors, and seek to identify cases of hematological malignancy...
September 2014: Familial Cancer
https://www.readbyqxmd.com/read/24735963/the-role-of-htlv-1-clonality-proviral-structure-and-genomic-integration-site-in-adult-t-cell-leukemia-lymphoma
#18
Lucy B Cook, Anat Melamed, Heather Niederer, Mikel Valganon, Daniel Laydon, Letizia Foroni, Graham P Taylor, Masao Matsuoka, Charles R M Bangham
Adult T-cell leukemia/lymphoma (ATL) occurs in ∼5% of human T-lymphotropic virus type 1 (HTLV-1)-infected individuals and is conventionally thought to be a monoclonal disease in which a single HTLV-1(+) T-cell clone progressively outcompetes others and undergoes malignant transformation. Here, using a sensitive high-throughput method, we quantified clonality in 197 ATL cases, identified genomic characteristics of the proviral integration sites in malignant and nonmalignant clones, and investigated the proviral features (genomic structure and 5' long terminal repeat methylation) that determine its capacity to express the HTLV-1 oncoprotein Tax...
June 19, 2014: Blood
https://www.readbyqxmd.com/read/24707948/10p12-31-12-2-variants-and-risk-of-childhood-acute-lymphoblastic-leukemia-in-a-chinese-population
#19
Jianping Deng, Yao Xue, Yaping Wang, Jing Chen, Jie Li, Qin Lu, Meilin Wang, Na Tong, Zhengdong Zhang, Yongjun Fang
Acute lymphoblastic leukemia (ALL) is a clonal hematologic disease, and is the most common cause of childhood malignancy. Recently, a new locus was identified at 10p12.31-12.2 through a genome-wide association study (GWAS) that included racially and ethnically diverse populations. We conducted a replication study with 570 cases of ALL and 673 cancer-free controls to validated the association of this locus with ALL susceptibility in a Chinese population. The results of our study confirmed that the 10p12.31-12...
January 2015: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/24558024/prediagnostic-transcriptomic-markers-of-chronic-lymphocytic-leukemia-reveal-perturbations-10-years-before-diagnosis
#20
M Chadeau-Hyam, R C H Vermeulen, D G A J Hebels, R Castagné, G Campanella, L Portengen, R S Kelly, I A Bergdahl, B Melin, G Hallmans, D Palli, V Krogh, R Tumino, C Sacerdote, S Panico, T M C M de Kok, M T Smith, J C S Kleinjans, P Vineis, S A Kyrtopoulos
BACKGROUND: B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms. METHODS: We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts...
May 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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