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Hyperdiploidy

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https://www.readbyqxmd.com/read/28500740/children-with-low-risk-acute-lymphoblastic-leukemia-are-at-highest-risk-of-second-cancers
#1
Stine N Nielsen, Frank Eriksson, Susanne Rosthoej, Mette K Andersen, Erik Forestier, Henrik Hasle, Lisa L Hjalgrim, Ann Aasberg, Jonas Abrahamsson, Mats Heyman, Ólafur G Jónsson, Kaie Pruunsild, Goda E Vaitkeviciené, Kim Vettenranta, Kjeld Schmiegelow
BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]...
May 13, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28436581/pediatric-acute-lymphoblastic-leukemia-with-t-1-19-tcf3-pbx1-in-taiwan
#2
Hsiu-Ju Yen, Shih-Hsiang Chen, Tsung-Yen Chang, Chao-Ping Yang, Dong-Tsamn Lin, Iou-Jih Hung, Kai-Hsin Lin, Jiann-Shiuh Chen, Chih-Cheng Hsiao, Tai-Tsung Chang, Te-Kao Chang, Ching-Tien Peng, Ming-Tsan Lin, Tang-Her Jaing, Hsi-Che Liu, Shiann-Tarng Jou, Meng-Yao Lu, Chao-Neng Cheng, Jiunn-Ming Sheen, Shyh-Shin Chiou, Giun-Yi Hung, Kang-Hsi Wu, Ting-Chi Yeh, Shih-Chung Wang, Rong-Long Chen, Hsiu-Hao Chang, Yung-Li Yang, Shu-Huey Chen, Shin-Nan Cheng, Yu-Hsiang Chang, Bow-Wen Chen, Yuh-Lin Hsieh, Fang-Liang Huang, Wan-Ling Ho, Jinn-Li Wang, Chia-Yau Chang, Yu-Hua Chao, Pei-Chin Lin, Yu-Chieh Chen, Yu-Mei Liao, Tung-Huei Lin, Lee-Yung Shih, Der-Cherng Liang
BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28389531/chk1-targeted-therapy-to-deplete-dna-replication-stressed-p53-deficient-hyperdiploid-colorectal-cancer-stem-cells
#3
Gwenola Manic, Michele Signore, Antonella Sistigu, Giorgio Russo, Francesca Corradi, Silvia Siteni, Martina Musella, Sara Vitale, Maria Laura De Angelis, Matteo Pallocca, Carla Azzurra Amoreo, Francesca Sperati, Simone Di Franco, Sabina Barresi, Eleonora Policicchio, Gabriele De Luca, Francesca De Nicola, Marcella Mottolese, Ann Zeuner, Maurizio Fanciulli, Giorgio Stassi, Marcello Maugeri-Saccà, Marta Baiocchi, Marco Tartaglia, Ilio Vitale, Ruggero De Maria
OBJECTIVE: Cancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies. DESIGN: To discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients...
April 7, 2017: Gut
https://www.readbyqxmd.com/read/28297630/genomics-of-multiple-myeloma
#4
Sebastien Robiou du Pont, Alice Cleynen, Charlotte Fontan, Michel Attal, Nikhil Munshi, Jill Corre, Hervé Avet-Loiseau
Multiple myeloma (MM) is characterized by wide variability in the chromosomal/genetic changes present in tumor plasma cells. Genetically, MM can be divided into two groups according to ploidy and hyperdiploidy versus nonhyperdiploidy. Several studies in gene expression profiling attempted to identify subentities in MM without convincing results. These studies mostly confirmed the cytogenetic data and subclassified patients according to 14q32 translocations and ploidy. More-recent data that are based on whole-exome sequencing have confirmed this heterogeneity and show many gene mutations but without a unifying mutation...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28256461/observation-on-frequency-clinico-pathological-significance-of-various-cytogenetic-risk-groups-in-multiple-myeloma-an-experience-from-india
#5
Pratibha S Kadam Amare, Hemani Jain, Shraddha Nikalje, Manju Sengar, Hari Menon, Nitin Inamdar, P G Subramanian, Sumeet Gujral, Tanuja Shet, Sridhar Epari, Reena Nair
BACKGROUND & OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy characterized by cytogenetic heterogeneity. In comparison with conventional karyotyping, fluorescence in situ hybridization (FISH) can efficiently detect various genetic changes in non-cycling plasma cells in 50-90 per cent of MM cases. The present study was undertaken in MM patients to evaluate the frequency and clinico-pathological significance of various cytogenetic abnormalities in the Indian population. METHODS: Interphase FISH was applied on purified plasma cells of 475 patients with MM using specific probes...
October 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#6
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27717146/hyperdiploidy-as-a-rare-event-that-accompanies-poor-prognosis-markers-in-cll
#7
Isabel González-Gascón Y Marín, Ana África Martín, María Hernández-Sanchez, Cristina Robledo, María Lourdes Hermosín, Natalia de Las Heras, Laura Lacalle, Josefina Galende, Felipe de Arriba, Ana Eugenia Rodríguez-Vicente, José-Ángel Hernández, Jesús María Hernández-Rivas
The presence of chromosomal gains other than trisomy 12 in chronic lymphocytic leukaemia (CLL) is unusual. However, some patients may show gains on several chromosomes simultaneously suggesting a hyperdiploid karyotype. OBJECTIVE: The objective of this study was to analyse by FISH the frequency and prognostic impact of hyperdiploidy in CLL. METHOD: A review of 1359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution was carried out...
February 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/27698447/long-term-outcome-of-6-month-maintenance-chemotherapy-for-acute-lymphoblastic-leukemia-in-children
#8
M Kato, S Ishimaru, M Seki, K Yoshida, Y Shiraishi, K Chiba, N Kakiuchi, Y Sato, H Ueno, H Tanaka, T Inukai, D Tomizawa, D Hasegawa, T Osumi, Y Arakawa, T Aoki, M Okuya, K Kaizu, K Kato, Y Taneyama, H Goto, T Taki, M Takagi, M Sanada, K Koh, J Takita, S Miyano, S Ogawa, A Ohara, M Tsuchida, A Manabe
In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear...
October 25, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27696391/prognostic-impact-of-pretreatment-cytogenetics-in-adult-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-in-the-era-of-minimal-residual-disease
#9
Ghayas C Issa, Hagop M Kantarjian, C Cameron Yin, Wei Qiao, Farhad Ravandi, Deborah Thomas, Nicholas J Short, Koji Sasaki, Guillermo Garcia-Manero, Tapan M Kadia, Jorge E Cortes, Naval Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Issa Khouri, Partow Kebriaei, Richard E Champlin, Sherry Pierce, Susan M O'Brien, Elias Jabbour
BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome-negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone-based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen...
February 1, 2017: Cancer
https://www.readbyqxmd.com/read/27683039/clonal-and-microclonal-mutational-heterogeneity-in-high-hyperdiploid-acute-lymphoblastic-leukemia
#10
Adam J de Smith, Juhi Ojha, Stephen S Francis, Erica Sanders, Alyson A Endicott, Helen M Hansen, Ivan Smirnov, Amanda M Termuhlen, Kyle M Walsh, Catherine Metayer, Joseph L Wiemels
High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment-related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4)...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27614666/genomic-copy-number-analysis-of-her2-equivocal-breast-cancers
#11
Katherine B Geiersbach, Carlynn Willmore-Payne, Alexandra V Pasi, Christian N Paxton, Theresa L Werner, Xinjie Xu, Carl T Wittwer, H Evin Gulbahce, Erinn Downs-Kelly
OBJECTIVES: Guidelines for HER2 testing define an equivocal range for HER2 using two approved testing methods, immunohistochemistry (IHC) and in situ hybridization (ISH). We investigated genome-wide copy number alterations in this subgroup. METHODS: Ten breast cancers with equivocal HER2 status by both IHC and ISH were analyzed by single-nucleotide polymorphism cytogenomic microarray (SNP array). DNA ploidy analysis by flow cytometry was performed on nine cases with sufficient material remaining...
October 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27560110/clinical-impact-of-minimal-residual-disease-in-children-with-different-subtypes-of-acute-lymphoblastic-leukemia-treated-with-response-adapted-therapy
#12
C-H Pui, D Pei, S C Raimondi, E Coustan-Smith, S Jeha, C Cheng, W P Bowman, J T Sandlund, R C Ribeiro, J E Rubnitz, H Inaba, T A Gruber, W H Leung, J J Yang, J R Downing, W E Evans, M V Relling, D Campana
To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27508939/baseline-characteristics-chromosomal-alterations-and-treatment-affecting-prognosis-of-deletion-17p-in-newly-diagnosed-myeloma
#13
Maximilian Merz, Thomas Hielscher, Anja Seckinger, Dirk Hose, Elias K Mai, Marc S Raab, Hartmut Goldschmidt, Anna Jauch, Jens Hillengass
Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some patients show long-term survival. With the current study we intended to identify factors impacting outcome of such high risk patients. We analyzed 110 newly diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ hybridization (FISH) in CD138-purified myeloma cells to identify prognostic factors for survival. Age >65 years, ISS III, and elevated LDH negatively impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had longer progression-free survival (PFS) than patients with del(17p) in >60% of plasma cells (26 vs...
November 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27463364/treatment-of-children-with-acute-lymphoblastic-leukemia-with-risk-group-based-intensification-and-omission-of-cranial-irradiation-a-korean-study-of-295-patients
#14
Jae Wook Lee, Seong-Koo Kim, Pil-Sang Jang, Dae-Chul Jeong, Nack-Gyun Chung, Bin Cho, Hack-Ki Kim
BACKGROUND: Recent studies indicate 70-80% event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL). In this study, we report the outcome of 295 children and adolescents treated at our institution, with stratification into four risk groups, and omission of cranial irradiation in all patients. PROCEDURE: Patients were diagnosed from January 2005 to December 2011 and classified and treated as low, standard, high, and very high risk groups. A delayed intensification phase was given twice for high and very high risk groups...
November 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27393278/prognostic-impact-of-runx1-and-etv6-gene-copy-number-on-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia-with-or-without-hyperdiploidy
#15
Nuket Yurur Kutlay, Esra Pekpak, Sule Altıner, Talia Ileri, Arzu Nedime Vicdan, Handan Dinçaslan, Elif Unal Ince, Fatma Ajlan Tukun
The ETV6/RUNX1 fusion gene is a valuable prognostic marker that is frequently observed in B-cell precursor acute lymphoblastic leukemia (B-cell ALL). However, the clinical significance of copy number aberrations in these genes remains unclear. In this study, the effects of various aberrations inETV6 and RUNX1 gene copy number on disease prognosis were evaluated in 21 pediatric patients diagnosed with B-cell ALL with/without t(12;21). The prognostic significance of changes in gene copy number of ETV6 or RUNX1 in the presence or absence of hyperdiploidy, trisomy 21, and t(12;21) translocation were also evaluated...
September 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27382557/a-retrospective-analysis-of-cytogenetic-alterations-in-patients-with-newly-diagnosed-multiple-myeloma-a-single-center-study-in-korea
#16
Shuhua Li, Hyeon-Ho Lim, Kwang-Sook Woo, Sung-Hyun Kim, Jin-Yeong Han
BACKGROUND: The accurate identification of cytogenetic abnormalities in multiple myeloma (MM) has become more important over recent years for the development of new diagnostic and prognostic markers. In this study, we retrospectively analyzed the cytogenetic aberrations in MM cases as an initial assessment in a single institute. METHODS: We reviewed the cytogenetic results from 222 patients who were newly diagnosed with MM between January 2000 and December 2015...
June 2016: Blood Research
https://www.readbyqxmd.com/read/27341996/chromosomal-aberrations-in-childhood-acute-lymphoblastic-leukemia-15-year-single-center-experience
#17
Marie Jarosova, Jana Volejnikova, Ilona Porizkova, Milena Holzerova, Dagmar Pospisilova, Zbynek Novak, Jana Vrbkova, Vladimir Mihal
Genetic analysis of leukemic cells significantly impacts prognosis and treatment stratification in childhood acute lymphoblastic leukemia (ALL). Our retrospective single center study of 86 children with ALL enrolled into three consecutive treatment protocols (ALL-BFM 90, ALL-BFM 95 and ALL IC-BFM 2002) between 1991 and 2007 demonstrates the importance of conventional cytogenetics and fluorescence in situ hybridization (FISH). Cytogenetic and FISH examinations were performed successfully in 82/86 (95.3%) patients and chromosomal changes were detected in 78 of the 82 (95...
July 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27229005/integration-of-genetic-and-clinical-risk-factors-improves-prognostication-in-relapsed-childhood-b-cell-precursor-acute-lymphoblastic-leukemia
#18
Julie A E Irving, Amir Enshaei, Catriona A Parker, Rosemary Sutton, Roland P Kuiper, Amy Erhorn, Lynne Minto, Nicola C Venn, Tamara Law, Jiangyan Yu, Claire Schwab, Rosanna Davies, Elizabeth Matheson, Alysia Davies, Edwin Sonneveld, Monique L den Boer, Sharon B Love, Christine J Harrison, Peter M Hoogerbrugge, Tamas Revesz, Vaskar Saha, Anthony V Moorman
Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < ...
August 18, 2016: Blood
https://www.readbyqxmd.com/read/27161658/genome-wide-single-nucleotide-polymorphism-array-analysis-improves-prognostication-of-acute-lymphoblastic-leukemia-lymphoma
#19
Yunhong Wang, Sue Miller, Diane Roulston, Dale Bixby, Lina Shao
Chromosomal abnormalities are important for the risk stratification of acute lymphoblastic leukemia/lymphoma (ALL). However, approximately 30% of pediatric and 50% of adult patients lack abnormalities with clinical relevance by traditional cytogenetic analysis. We integrated cytogenetic, fluorescence in situ hybridization, and whole-genome single-nucleotide polymorphism array results from 60 consecutive clinical ALL cases. By cytogenetic and/or fluorescence in situ hybridization analyses, recurring abnormalities with clinical relevance were observed in 33 B-cell ALL (B-ALL), including t(9;22), hyperdiploidy, KMT2A translocation, ETV6-RUNX1, intrachromosomal amplification of chromosome 21, near haploidy or low hypodiploidy, and t(8;22)...
July 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27157252/genomewide-profiling-of-copy-number-alteration-in-monoclonal-gammopathy-of-undetermined-significance
#20
Aneta Mikulasova, Jan Smetana, Marketa Wayhelova, Helena Janyskova, Viera Sandecka, Zuzana Kufova, Martina Almasi, Jiri Jarkovsky, Evzen Gregora, Petr Kessler, Marek Wrobel, Brian A Walker, Christopher P Wardell, Gareth J Morgan, Roman Hajek, Petr Kuglik
Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10(-5) ) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1...
December 2016: European Journal of Haematology
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