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https://www.readbyqxmd.com/read/28646637/ts-gene-polymorphisms-correlate-with-susceptibility-to-acute-lymphocytic-leukemia-in-children
#1
Runyin Zou, Xiangling He, Yanpeng Wu, Xin Tian, Yalan You, Mincui Zheng, Wanli Li, Hui Zou, Hua Liu, Xiujuan Zhu, Chengguang Zhu
BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups...
June 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28642592/integrative-network-analysis-identifies-novel-drivers-of-pathogenesis-and-progression-in-newly-diagnosed-multiple-myeloma
#2
A Laganà, D Perumal, D Melnekoff, B Readhead, B A Kidd, V Leshchenko, P-Y Kuo, J Keats, M DeRome, J Yesil, D Auclair, S Lonial, A Chari, H J Cho, B Barlogie, S Jagannath, J T Dudley, S Parekh
Multiple Myeloma (MM) is an incurable malignancy of bone marrow plasma cells characterized by wide clinical and molecular heterogeneity. In this study we applied an integrative network biology approach to molecular and clinical data measured from 450 patients with newly diagnosed MM from the MMRF CoMMpass study. A novel network model of myeloma (MMNet) was constructed, revealing complex molecular disease patterns and novel associations between clinical traits and genomic markers. Genomic alterations and groups of co-expressed genes correlate with disease stage, tumor clonality, and early progression...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28641468/association-between-immunoglobulin-heavy-chain-variable-region-mutational-status-and-isolated-favorable-baseline-genomic-aberrations-in-chronic-lymphocytic-leukemia
#3
Jose D Sandoval-Sus, Julio C Chavez, Samir Dalia, Syeda Mahrukh Hussnain Naqvi, Chetasi Talati, Lisa Nodzon, Mohamed A Kharfan-Dabaja, Javier Pinilla-Ibarz
Immunoglobulin heavy-chain variable region (IGHV) mutational status and karyotype abnormalities are important prognostic factors in chronic lymphocytic leukemia (CLL). The goal was to assess the impact of IGHV in CLL patients with isolated favorable genetic aberrations (del13q, trisomy 12, or negative fluorescence in situ hybridization [FISH]). We studied 273 CLL patients with both IGHV mutational status and cytogenetic information: 145 with isolated del13q 49 with sole trisomy 12 and 79 with negative FISH...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28641145/lack-of-association-between-deletion-polymorphism-of-bim-gene-and-in-vitro-drug-sensitivity-in-b-cell-precursor-acute-lymphoblastic-leukemia
#4
Meixian Huang, Kunio Miyake, Keiko Kagami, Masako Abe, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Nobutaka Kiyokawa, Kanji Sugita, Takeshi Inukai
A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy...
June 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28640831/ribosomal-dna-copy-number-loss-and-sequence-variation-in-cancer
#5
Baoshan Xu, Hua Li, John M Perry, Vijay Pratap Singh, Jay Unruh, Zulin Yu, Musinu Zakari, William McDowell, Linheng Li, Jennifer L Gerton
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28640357/rna-sequencing-of-esophageal-adenocarcinomas-identifies-novel-fusion-transcripts-including-npc1-melk-arising-from-a-complex-chromosomal-rearrangement
#6
Zhixiong Wang, Yulan Cheng, John M Abraham, Rong Yan, Xi Liu, Wei Chen, Sariat Ibrahim, Gary P Schroth, Xiquan Ke, Yulong He, Stephen J Meltzer
BACKGROUND: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). METHODS: To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28638735/maternal-microchimerism-is-prevalent-in-cord-blood-in-memory-t-cells-and-other-cell-subsets-and-persists-post-transplant
#7
Sami B Kanaan, Hilary S Gammill, Whitney E Harrington, Stephen C De Rosa, Philip A Stevenson, Alexandra M Forsyth, Judy Allen, Emma Cousin, Koen van Besien, Colleen S Delaney, J Lee Nelson
Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28632001/vasodilator-responsiveness-in-idiopathic-pulmonary-arterial-hypertension-identifying-a-distinct-phenotype-with-distinct-physiology-and-distinct-prognosis
#8
David Langleben, Stylianos Orfanos
Within the cohort of patients suffering from idiopathic pulmonary arterial hypertension (IPAH) is a group that responds dramatically (VR-PAH) to an acute vasodilator challenge and that has excellent long-term hemodynamic improvement and prognosis on high dose calcium channel blockers compared with vasodilator non-responders (VN-PAH). For the purposes of diagnosing VR-PAH, there is to date no test to replace the acute vasodilator challenge. However, recent studies have identified markers that may aid in the identification of VR-PAH, including peripheral blood lymphocyte RNA expression levels of desmogelin-2 and Ras homolog gene family member Q, and plasma levels of provirus integration site for Moloney murine leukemia virus...
June 20, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28631637/an-integrated-genomic-profile-that-includes-copy-number-alterations-is-highly-predictive-of-minimal-residual-disease-status-in-childhood-precursor-b-lineage-acute-lymphoblastic-leukemia
#9
Nikhil Patkar, P G Subramanian, Prashant Tembhare, Sneha Mandalia, Gaurav Chaterjee, Nikhil Rabade, Rohan Kodgule, Karishma Chopra, Asma Bibi, Swapnali Joshi, Shruti Chaudhary, Russel Mascerhenas, Pratibha Kadam-Amare, Gaurav Narula, Brijesh Arora, Shripad Banavali, Sumeet Gujral
INTRODUCTION: Copy number alterations (CNA) have been described in childhood precursor B-lineage acute lymphoblastic leukemia (B-ALL) which in conjunction with chromosomal abnormalities drive leukemogenesis. There is no consensus on the clinical incorporation of CNA in B-ALL. An integrated genomic classification (IGC) has been proposed which includes CNA and cytogenetics. METHODS: We correlated this IGC with immunophenotypic minimal residual disease (MRD) as well as other standard criteria for 245 patients of B-ALL such as National Cancer Institute (NCI) risk, D+8 prednisolone response, cytogenetics, and ploidy status...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28630052/infection-exposure-promotes-etv6-runx1-precursor-b-cell-leukemia-via-impaired-h3k4-demethylases
#10
Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Ines Gonzalez-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René M Linka, Marta Garcia-Suquia, María V Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begona Garcia-Cenador, Francisco Javier Garcia-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28628558/genetics-of-pleiotropic-effects-of-dexamethasone
#11
Laura B Ramsey, Stan Pounds, Cheng Cheng, Xueyuan Cao, Wenjian Yang, Colton Smith, Seth E Karol, Chengcheng Liu, John C Panetta, Hiroto Inaba, Jeffrey E Rubnitz, Monika L Metzger, Raul C Ribeiro, John T Sandlund, Sima Jeha, Ching-Hon Pui, William E Evans, Mary V Relling
OBJECTIVES: Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia...
June 16, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28627443/impact-of-the-bcr-abl1-fusion-transcripts-on-different-responses-to-imatinib-and-disease-recurrence-in-iranian-patients-with-chronic-myeloid-leukemia
#12
Golale Rostami, Mohammad Hamid, Hasan Jalaeikhoo
BACKGROUND: One genomic breakpoint can result in variable BCR-ABL1 transcript types due to alternative splicing. The influence of different BCR-ABL1 transcript types on clinical outcome is still controversial. AIM OF THE STUDY: The objective of this analysis was to determine the impact of transcript type on response, clinical outcome, recurrence risk after treatment with Imatinib mesylate in Chronic Myeloid Leukemia (CML) patients. METHODS: Sixty CML patients in chronic phase were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and banding standard protocols...
June 13, 2017: Gene
https://www.readbyqxmd.com/read/28626802/cohesin-mutations-in-myeloid-malignancies
#13
Joseph B Fisher, Maureen McNulty, Michael J Burke, John D Crispino, Sridhar Rao
Acute Myeloid Leukemia (AML) is a hematologic malignancy with a poor prognosis. Recent genome-wide sequencing studies have identified frequent mutations in genes encoding members of the cohesin complex. Mutations in cohesin contribute to myeloid malignancies by conferring enhanced self-renewal of hematopoietic stem and progenitor cells but the mechanisms behind this phenotype have not been fully elucidated. Of note, cohesin mutations are highly prevalent in acute megakaryocytic leukemia associated with Down syndrome (DS-AMKL), where they occur in over half of patients...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#14
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28615198/polymorphic-nature-of-htlv-1-particle-cores-as-revealed-through-characterization-of-a-chronically-infected-cell-line
#15
Morgan E Meissner, Luiza Mendonça, Wei Zhang, Louis M Mansky
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 cell-to-cell transmission is dependent on the release of infectious virus particles into the virological synapse. HTLV-1 particle structure is still poorly understood, and previous studies have analyzed viruses produced by transformed lymphocytic cell lines chronically infected with HTLV-1, particularly the MT-2 cell line, which harbors truncated proviruses and expresses aberrant forms of the Gag protein...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28606096/pan-cancer-analysis-reveals-technical-artifacts-in-tcga-germline-variant-calls
#16
Alexandra R Buckley, Kristopher A Standish, Kunal Bhutani, Trey Ideker, Roger S Lasken, Hannah Carter, Olivier Harismendy, Nicholas J Schork
BACKGROUND: Cancer research to date has largely focused on somatically acquired genetic aberrations. In contrast, the degree to which germline, or inherited, variation contributes to tumorigenesis remains unclear, possibly due to a lack of accessible germline variant data. Here we called germline variants on 9618 cases from The Cancer Genome Atlas (TCGA) database representing 31 cancer types. RESULTS: We identified batch effects affecting loss of function (LOF) variant calls that can be traced back to differences in the way the sequence data were generated both within and across cancer types...
June 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28605390/retroviral-scanning-mapping-mlv-integration-sites-to-define-cell-specific-regulatory-regions
#17
Oriana Romano, Ingrid Cifola, Valentina Poletti, Marco Severgnini, Clelia Peano, Gianluca De Bellis, Fulvio Mavilio, Annarita Miccio
Moloney murine leukemia (MLV) virus-based retroviral vectors integrate predominantly in acetylated enhancers and promoters. For this reason, mLV integration sites can be used as functional markers of active regulatory elements. Here, we present a retroviral scanning tool, which allows the genome-wide identification of cell-specific enhancers and promoters. Briefly, the target cell population is transduced with an mLV-derived vector and genomic DNA is digested with a frequently cutting restriction enzyme. After ligation of genomic fragments with a compatible DNA linker, linker-mediated polymerase chain reaction (LM-PCR) allows the amplification of the virus-host genome junctions...
May 28, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28604954/-detection-of-genomic-abnormalities-among-105-patients-with-chronic-lymphocytic-leukemia-using-fluorescence-in-situ-hybridization
#18
Huanping Wang, Huan Xu, Zhimei Chen, Jiyu Lou, Jie Jin
OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL). METHODS: Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated. RESULTS: The FISH assay has detected genomic abnormalities in 81 (77...
June 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28602946/whole-genome-analysis-reveals-unexpected-dynamics-of-mutant-subclone-development-in-a-patient-with-jak2-v617f-positive-chronic-myeloid-leukemia
#19
I Sloma, M Mitjavila-Garcia, O Feraud, F Griscelli, N Oudrhiri, S El Marsafy, E Gobbo, D Divers, A Proust, D M Smadja, C Desterke, A Carles, Y Ma, M Hirst, M A Marra, C J Eaves, A Bennaceur-Griscelli, A G Turhan
We report here the first use of whole genome sequencing (WGS) to examine the initial clonal dynamics in an unusual patient with chronic myeloid leukemia (CML) who presented in chronic phase (CP) with doubly marked BCR-ABL1(+)/JAK2(V617F)-mutant cells and over a 9 year period progressed into an accelerated phase (AP) and then terminal blast phase (BP). WGS showed the diagnostic cells also contained mutations in ASXL1, SEC23B, MAD1L1 and RREB1, as well as 12,000 additional uncommon DNA variants. WGS of endothelial cells generated from circulating precursors revealed many of these were shared with the CML clone...
June 7, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28602756/antrodia-cinnamomea-sensitizes-radio-chemo-therapy-of-cancer-stem-like-cells-by-modulating-microrna-expression
#20
Yu-Kai Su, Ping-Hsiao Shih, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T H Wu, Chun-Chih Huang, Yew-Min Tzeng, Michael Hsiao, Chi-Tai Yeh, Chien-Min Lin
ETHNOPHARMACOLOGICAL RELEVANCE: The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention...
June 8, 2017: Journal of Ethnopharmacology
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