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17p deletion

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https://www.readbyqxmd.com/read/28641639/-clinical-features-and-response-to-treatment-in-newly-diagnosed-multiple-myeloma-patients-with-deletion-17p
#1
Yan Liu, Xiao-Yan Ke, Jing Wang, Yan-Fang Wang, Fei Dong, Lei Tian, Wei Wan, Hong-Mei Jing
OBJECTIVE: To investigate the clinical features and response to therapies in multiple myeloma (MM) patients with del (17p). METHODS: A total of 122 newly diagnosed MM patients hospitalized in the Department of Hematology of Peking University Third Hospital between October 2012 and September 2016 were analyzed retrospectively. The fluorescent in situ hybridization(FISH) and G-binding staining were used for detection of cytogenetic abnormalities. These MM patients with del (17p) were divided into non-bortezomib chemotherapy (VAD or CHOP) group and bortezomib chemotherapy (PAD or PCD) group...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28625614/characterization-of-an-acquired-jumping-translocation-involving-3q13-31-qter-in-a-patient-with-de-novo-acute-monocytic-leukemia
#2
Eigil Kjeldsen
We studied an adult with de novo acute monocytic leukemia and a dismal outcome where her leukemic cells harbored an acquired rare jumping translocation (JT). We used oligo-based array CGH (oaCGH) analysis, fluorescence in situ hybridization (FISH), and 24-color karyotyping to enhance the characterization of the JT. G-banding detected a JT involving the 3q13.3-qter chromosomal segment and the recipient chromosomal regions 17p, 8q, and 15q. Each clone with JT was associated with trisomy 8. oaCGH analysis revealed an additional submicroscopic deletion in 3q13...
June 15, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28621320/genomic-analysis-of-follicular-dendritic-cell-sarcoma-by-molecular-inversion-probe-array-reveals-tumor-suppressor-driven-biology
#3
Erica F Andersen, Christian N Paxton, Dennis P O'Malley, Abner Louissaint, Jason L Hornick, Gabriel K Griffin, Yuri Fedoriw, Young S Kim, Lawrence M Weiss, Sherrie L Perkins, Sarah T South
Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28605616/managing-patients-with-tp53-deficient-chronic-lymphocytic-leukemia
#4
Jennifer Edelmann, John G Gribben
Patients with chronic lymphocytic leukemia (CLL) having a chromosomal loss on the short arm of chromosome 17 including the TP53 gene locus (17p deletion) and/or having mutations in TP53 have a short overall survival and, until recently, limited treatment options. The recent introduction of two novel substance classes, B-cell receptor inhibitors and BH3 mimetics, into CLL treatment has provided enormous clinical progress in this previously difficult-to-treat patient subgroup characterized by high risk for treatment failure with standard chemoimmunotherapy and rapid disease progression...
June 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28604954/-detection-of-genomic-abnormalities-among-105-patients-with-chronic-lymphocytic-leukemia-using-fluorescence-in-situ-hybridization
#5
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/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1-905-trial-patients
#6
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28578655/potential-mechanisms-of-resistance-to-venetoclax-and-strategies-to-circumvent-it
#7
Stephen K Tahir, Morey L Smith, Paul Hessler, Lisa Roberts Rapp, Kenneth B Idler, Chang H Park, Joel D Leverson, Lloyd T Lam
BACKGROUND: Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges...
June 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28562380/pharmacokinetics-of-venetoclax-in-patients-with-17p-deletion-chronic-lymphocytic-leukemia
#8
Ahmed Hamed Salem, Martin Dunbar, Suresh K Agarwal
Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal...
May 30, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28559149/chronic-lymphocytic-leukemia-patients-with-deletion-11q-have-a-short-time-to-requirement-of-first-line-therapy-but-long-overall-survival-results-of-a-population-based-cohort-in-british-columbia-canada
#9
Jennifer Goy, Tanya L Gillan, Helene Bruyere, Steven J T Huang, Monica Hrynchak, Aly Karsan, Khaled Ramadan, Joseph Connors, Cynthia L Toze, Alina S Gerrie
BACKGROUND: Chronic lymphocytic leukemia (CLL) patients with 11q22.3 deletion (11q-) have an aggressive clinical course, and thus selection of first-line therapy in this group is important. This study aimed to improve our understanding of real-world practice patterns and outcomes of CLL patients with 11q- in a population-based setting. PATIENTS AND METHODS: The British Columbia CLL Database was used to identify patients with 11q-. Overall survival (OS) and treatment-free survival (TFS) were assessed after adjustment for prognostic factors...
May 8, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28550191/the-level-of-deletion-17p-and-bi-allelic-inactivation-of-tp53-has-a-significant-impact-on-clinical-outcome-in-multiple-myeloma
#10
Sharmilan Thanendrarajan, Erming Tian, Pingping Qu, Pankaj Mathur, Carolina Schinke, Frits van Rhee, Maurizio Zangari, Leo Rasche, Niels Weinhold, Daisy Alapat, William Bellamy, Cody Ashby, Sandra Mattox, Joshua Epstein, Shmuel Yaccoby, Bart Barlogie, Antje Hoering, Michael Bauer, Brian A Walker, Faith E Davies, Gareth J Morgan
No abstract text is available yet for this article.
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28536495/serum-ldh-level-may-predict-outcome-of-chronic-lymphocytic-leukemia-patients-with-a-17p-deletion-a-retrospective-analysis-of-prognostic-factors-in-china
#11
Heng Li, Wenjie Xiong, Huimin Liu, Shuhua Yi, Zhen Yu, Wei Liu, Rui Lyu, Tingyu Wang, Dehui Zou, Zengjun Li, Lugui Qiu
OBJECTIVE: This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia (CLL) and a 17p deletion (17p-) and identify the predictive factors within this subgroup. METHODS: The sample of patients with CLL were analyzed by fluorescencein situ hybridization for deletions in chromosome bands 11q22, 13q14 and 17p13; trisomy of bands 12q13; and translocation involving band 14q32. The data from 456 patients with or without a 17p- were retrospectively collected and analyzed...
April 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28504856/cell-free-dna-copy-number-variations-in-plasma-from-colorectal-cancer-patients
#12
Jian Li, Rachel L Dittmar, Shu Xia, Huijuan Zhang, Meijun Du, Chiang-Ching Huang, Brooke R Druliner, Lisa Boardman, Liang Wang
To evaluate the clinical utility of cell-free DNA (cfDNA), we performed whole-genome sequencing to systematically examine plasma cfDNA copy number variations (CNVs) in a cohort of patients with colorectal cancer (CRC, n = 80), polyps (n = 20), and healthy controls (n = 35). We initially compared cfDNA yield in 20 paired serum-plasma samples and observed significantly higher cfDNA concentration in serum (median = 81.20 ng, range 7.18-500 ng·mL(-1) ) than in plasma (median = 5.09 ng, range 3.76-62...
May 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28498418/identification-and-expression-of-mmsa-8-and-its-clinical-significance-in-multiple-myeloma
#13
Rui He, Nan Yang, Pengyu Zhang, Jie Liu, Junhui Li, Fulin Zhou, Wanggang Zhang
In our previous studies, we identified 12 multiple myeloma (MM)-associated antigens by serological analysis of tumor-associated antigens with a recombinant cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A-related transcript variant 1 that is specifically associated with MM...
June 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495913/longitudinal-fluorescence-in-situ-hybridization-reveals-cytogenetic-evolution-in-myeloma-relapsing-after-autologous-transplantation
#14
Maximilian Merz, Anna Jauch, Thomas Hielscher, Elias K Mai, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc S Raab, Hans Salwender, Igor W Blau, Hans-Walter Lindemann, Ingo Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja Weisel, Hartmut Goldschmidt, Jens Hillengass
To investigate cytogenetic evolution after upfront autologous stem cell transplantation for newly diagnosed myeloma we retrospectively analyzed fluorescence in situ hybridization results of 128 patients with paired bone marrow samples at primary diagnosis and relapse. High-risk cytogenetic abnormalities (deletion 17p and/or gain1q21) occurred more frequently after relapse (odds ratio: 6.33; 95% confidence interval: 1.86,33.42;p<0.001). No significant changes were observed for defined IgH translocations (t(4;14); t(11;14); t(14;16)) or hyperdiploid karyotypes between primary diagnosis and relapse...
May 11, 2017: Haematologica
https://www.readbyqxmd.com/read/28492339/venetoclax-for-the-treatment-of-patients-with-chronic-lymphocytic-leukemia
#15
Jennifer Crombie, Matthew S Davids
Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp-up and close tumor lysis syndrome monitoring and prophylaxis...
May 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28459703/novel-cytogenetic-findings-in-a-case-of-mixed-phenotype-acute-leukemia-within-the-context-of-a-complex-karyotype
#16
David Shabsovich, Gary Schiller, Yalda Naeini, Robert Collins, Carlos A Tirado
BACKGROUND: Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy characterized by combinatorial aberrations involving cells of the myeloid, T-, and/or B- lineages, most often diagnosed by means of immunophenotyping in order to assess lineage-specific markers, which can still yield inconclusive diagnoses. MPAL with a complex karyotype (three or more chromosomal abnormalities) is a cytogenetic subtype of MPAL associated with a poor prognosis, but limited data is available about the cytogenetic abnormalities present in this context...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28446054/pharmacotherapy-of-relapsed-refractory-chronic-lymphocytic-leukemia
#17
Abdallah Abou Zahr, Prithviraj Bose, Michael J Keating
The treatment of relapsed/refractory (RR) CLL has been revolutionized by the advent of the new oral inhibitors of B-cell receptor (BCR) signaling and the pro-survival protein, B-cell lymphoma 2 (BCL2). Additionally, new and more potent monoclonal antibodies against CD20 have replaced/may replace rituximab in many settings. Areas covered: Herein, we review the entire therapeutic landscape of RR CLL, with particular attention to the new small-molecule kinase inhibitors and BH3-mimetics. We discuss preclinical data with these agents in CLL, cover available efficacy and safety information, and examine potential resistance mechanisms and possible rational combinations to circumvent them...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28439761/small-molecule-inhibitors-in-chronic-lymphocytic-lymphoma-and-b-cell-non-hodgkin-lymphoma
#18
REVIEW
Allison Rosenthal
PURPOSE OF REVIEW: The purpose of this review is to summarize the available literature for the use of small molecule inhibitors in chronic lymphocytic leukemia and B cell non-Hodgkin lymphoma. RECENT FINDINGS: Ibrutinib, idelalisib, and venetoclax are small molecule inhibitors that have revolutionized therapeutic options for patients with CLL, particularly for those with high-risk disease including 17p deletion. These drugs are increasingly finding application in a variety of subtypes of B cell NHL...
April 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28407731/segmentum-a-tool-for-copy-number-analysis-of-cancer-genomes
#19
Ebrahim Afyounian, Matti Annala, Matti Nykter
BACKGROUND: Somatic alterations, including loss of heterozygosity, can affect the expression of oncogenes and tumor suppressor genes. Whole genome sequencing enables detailed characterization of such aberrations. However, due to the limitations of current high throughput sequencing technologies, this task remains challenging. Hence, accurate and reliable detection of such events is crucial for the identification of cancer-related alterations. RESULTS: We introduce a new tool called Segmentum for determining somatic copy numbers using whole genome sequencing from paired tumor/normal samples...
April 13, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28398276/bcl-2-as-a-therapeutic-target-in-chronic-lymphocytic-leukemia
#20
REVIEW
Catherine Daniel, Anthony R Mato
Venetoclax (formerly ABT-199) was recently approved in the United States for the treatment of patients who have relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of CLL. The potency of venetoclax has been associated with a unique ability to induce deep (minimal residual disease-negative) complete remissions that appear to be durable...
March 2017: Clinical Advances in Hematology & Oncology: H&O
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