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https://www.readbyqxmd.com/read/28427204/an-extensive-molecular-cytogenetic-characterization-in-high-risk-chronic-lymphocytic-leukemia-identifies-karyotype-aberrations-and-tp53-disruption-as-predictors-of-outcome-and-chemorefractoriness
#1
Gian Matteo Rigolin, Luca Formigaro, Maurizio Cavallari, Francesca Maria Quaglia, Enrico Lista, Antonio Urso, Emanuele Guardalben, Sara Martinelli, Elena Saccenti, Cristian Bassi, Laura Lupini, Maria Antonella Bardi, Eleonora Volta, Elisa Tammiso, Aurora Melandri, Massimo Negrini, Francesco Cavazzini, Antonio Cuneo
We investigated whether karyotype analysis and mutational screening by next generation sequencing could predict outcome in 101 newly diagnosed chronic lymphocytic leukemia patients with high-risk features, as defined by the presence of unmutated IGHV gene and/or 11q22/17p13 deletion by FISH and/or TP53 mutations. Cytogenetic analysis showed favorable findings (normal karyotype and isolated 13q14 deletion) in 30 patients, unfavorable (complex karyotype and/or 17p13/11q22 deletion) in 34 cases and intermediate (all other abnormalities) in 36 cases...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424451/prognostic-impact-of-notch1-myd88-and-sf3b1-mutations-in-polish-population-of-chronic-lymphocytic-leukemia-patients
#2
Maciej Putowski, Marta Podgórniak, Marta Piróg, Joanna Knap, Joanna Zaleska, Joanna Purkot, Jacek Zawiślak, Ewelina Zakrzewska, Agnieszka Karczmarczyk, Paulina Własiuk, Edyta Subocz, Krzysztof Giannopoulos
INTRODUCTION    Currently available prognostic factors determining the course of chronic lymphocytic leukemia (CLL) are not fully efficient especially for newly diagnosed patients. Investigation of molecular changes may help to clarify the reasons of the heterogeneity of the disease. Apart from already confirmed TP53 mutations, novel lesions: NOTCH1, SF3B1 and MYD88 might represent biomarkers of clinical relevance.  OBJECTIVES    The aim was to evaluate mutational status of NOTCH1, MYD88 and SF3B1 and to compare results with confirmed prognostic factors: ZAP-70, CD38 and IGHV mutation...
April 20, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28424416/loss-of-thyroid-hormone-receptor-interactor-13-inhibits-cell-proliferation-and-survival-in-human-chronic-lymphocytic-leukemia
#3
Keshu Zhou, Wentao Zhang, Qing Zhang, Ruirui Gui, Huifang Zhao, Xiaofei Chai, Yufu Li, Xudong Wei, Yongping Song
BACKGROUND: The genetic regulation of apoptosis and cell proliferation plays a role in the growth of chronic lymphocytic leukemia (CLL), the most common form of leukemia in the Western hemisphere. Although thyroid hormone receptor interactors (TRIPs) are known to play roles in cell cycle, the potential involvement of the novel family member TRIP13 in CLL has not yet been investigated. METHODS: Quantitative PCR (qPCR) was used to detect expression of TRIP13 in 36 CLL patients and 33 healthy donors CD19+ B cells...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424415/clinicopathological-features-and-outcome-of-chronic-lymphocytic-leukaemia-in-chinese-patients
#4
Thomas Sau-Yan Chan, Yuh-Shan Lee, Ilaria Del Giudice, Marilisa Marinelli, Caterina Ilari, Luciana Cafforio, Anna Guarini, Daryl Tan, Colin Phipps, Yeow-Tee Goh, William Hwang, Allan Zhi-Kai Goh, Lisa Lai-Ping Siu, Saliangi Wu, Chun-Yin Ha, Shek-Ying Lin, Chi-Hang Kwok, Chi-Kuen Lau, Kit-Fai Wong, Robin Foà, Yok-Lam Kwong, Eric Tse
Chronic lymphocytic leukaemia (CLL) is uncommon in Chinese population and its biology, genetics and treatment outcome in Chinese patients have not been comprehensively investigated. In this study, we studied the clinicopathological features and outcome of 212 Chinese patients with newly diagnosed CLL in Hong Kong and Singapore. The median age at diagnosis was 64 years. The majority of patients presented with early-stage disease (Binet stage A, 56.1%). Del(13)(q14) was the most frequent abnormality (41.7%) detected by fluorescence in situ hybridization (FISH) analysis...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424162/pembrolizumab-in-patients-with-chronic-lymphocytic-leukemia-with-richter-s-transformation-and-relapsed-cll
#5
Wei Ding, Betsy R LaPlant, Timothy G Call, Sameer A Parikh, Jose F Leis, Rong He, Tait D Shanafelt, Sutapa Sinha, Jennifer Le-Rademacher, Andrew L Feldman, Thomas M Habermann, Thomas E Witzig, Gregory A Wiseman, Yi Lin, Erik Asmus, Grzegorz S Nowakowski, Michael J Conte, Deborah A Bowen, Casey N Aitken, Daniel L Van Dyke, Patricia T Greipp, Xin Liu, Xiaosheng Wu, Henan Zhang, Charla R Secreto, Shulan Tian, Esteban Braggio, Linda E Wellik, Ivana Micallef, David S Viswanatha, Huihuang Yan, Asher A Chanan-Khan, Neil E Kay, Haidong Dong, Stephen M Ansell
CLL patients progressed early on ibrutinib often develop Richter's transformation (RT) with short survival about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study MC1485 (NCT02332980) was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled and 60% received prior ibrutinib...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28423121/telomere-length-analysis-in-monoclonal-b-cell-lymphocytosis-and-chronic-lymphocytic-leukemia-binet-a
#6
F M Furtado, P S Scheucher, B A Santana, N F Scatena, R T Calado, E M Rego, D M Matos, R P Falcão
Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic clinical entity characterized by the proliferation of monoclonal B cells not meeting the diagnosis criteria for chronic lymphocytic leukemia (CLL). MBL may precede the development of CLL, but the molecular mechanisms responsible for disease progression and evolution are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. Here, we determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy volunteers...
April 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28422443/role-of-cd200-in-differential-diagnosis-of-mature-b-cell-neoplasm
#7
K Rahman, P Kumar, R Gupta, M K Singh, S Nityanand
INTRODUCTION: CD 200 is a type I immunoglobulin super family membrane glycoprotein, which is expressed in various mature B-cell neoplasm (MBN). This study aimed at analyzing the expression pattern of CD200 by flow cytometry immunophenotyping (FCI) and to evaluate its utility in narrowing down the differential diagnosis of MBN, particularly in low-grade lymphomas. METHODS: A total of 160 samples were evaluated by FCI over a period of 2 years (July 2014-June 2016), by a panel of antibodies including CD200...
April 19, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28421390/ofatumumab-combined-with-chlorambucil-for-previously-untreated-chronic-lymphocytic-leukemia-a-phase-i-ii-open-label-study-in-japan
#8
Kiyohiko Hatake, Michinori Ogura, Kohichi Takada, Masafumi Taniwaki, Fanghong Zhang, Taizo Fujita, Kiyoshi Ando
Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs...
April 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28419823/genetic-aspects-of-auto-immune-profiles-of-healthy-chickens
#9
Henk K Parmentier, Priscilla S van der Vaart, Mike G B Nieuwland, Huub F J Savelkoul
Auto-antibody profiles binding liver antigens differed between chicken lines divergently selected for specific antibody responses to SRBC, and were affected by ageing suggesting both genetic and environmental effects. Presence and levels of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in plasma at 5 weeks of age from 10 individual full sibs and their parents from 5 Hsrbc and 5 Lsrbc line families was studied to reveal genetic relations. Non-genetic maternal effects were studied by comparing auto-antibody profiles of 36 weeks old hens from 2 other unrelated lines with the profiles from their chicks at hatch...
April 15, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28419476/cortactin-a-lyn-substrate-is-a-checkpoint-molecule-at-the-intersection-of-bcr-and-cxcr4-signalling-pathway-in-chronic-lymphocytic-leukaemia-cells
#10
Veronica Martini, Cristina Gattazzo, Federica Frezzato, Valentina Trimarco, Marco Pizzi, Giorgia Chiodin, Filippo Severin, Edoardo Scomazzon, Vincenza Guzzardo, Deborah Saraggi, Flavia Raggi, Leonardo Martinello, Monica Facco, Andrea Visentin, Francesco Piazza, Anna Maria Brunati, Gianpietro Semenzato, Livio Trentin
Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28418900/therapeutic-inhibition-of-usp7-pten-network-in-chronic-lymphocytic-leukemia-a-strategy-to-overcome-tp53-mutated-deleted-clones
#11
Giovanna Carrà, Cristina Panuzzo, Davide Torti, Guido Parvis, Sabrina Crivellaro, Ubaldo Familiari, Marco Volante, Deborah Morena, Marcello Francesco Lingua, Mara Brancaccio, Angelo Guerrasio, Pier Paolo Pandolfi, Giuseppe Saglio, Riccardo Taulli, Alessandro Morotti
Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either indolent or aggressive clinical course. Current treatment regiments have significantly improved the overall outcomes even if higher risk subgroups - those harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p) - remain highly challenging. In the present work, we identified USP7, a known de-ubiquitinase with multiple roles in cellular homeostasis, as a potential therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2), an upstream interactor known to be deregulated in CLL; iii) effectively targeted by the USP7 inhibitor P5091...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416773/changes-in-t-cell-subpopulations-and-cytokine-network-during-early-period-of-ibrutinib-therapy-in-chronic-lymphocytic-leukemia-patients-the-significant-decrease-in-t-regulatory-cells-number
#12
Monika Podhorecka, Aneta Goracy, Agnieszka Szymczyk, Malgorzata Kowal, Blanca Ibanez, Olga Jankowska-Lecka, Arkadiusz Macheta, Aleksandra Nowaczynska, Elzbieta Drab-Urbanek, Sylwia Chocholska, Dariusz Jawniak, Marek Hus
B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412730/the-long-noncoding-rna-trerna-decreases-dna-damage-and-is-associated-with-poor-response-to-chemotherapy-in-chronic-lymphocytic-leukemia
#13
Cecelia R Miller, Amy S Ruppert, Sydney Fobare, Timothy L Chen, Chaomei Liu, Amy Lehman, James S Blachly, Xiaoli Zhang, David M Lucas, Michael R Grever, Martin S Tallman, Ian W Flinn, Laura Z Rassenti, Thomas J Kipps, Deepa Sampath, Kevin R Coombes, Erin K Hertlein
The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409640/polymer-pen-chemical-lift-off-lithography
#14
Xiaobin Xu, Qing Yang, Kevin M Cheung, Chuanzhen Zhao, Natcha Wattanatorn, Jason Nathaniel Belling, John M Abendroth, Liane S Slaughter, Chad A Mirkin, Anne M Andrews, Paul S Weiss
We designed and fabricated large arrays of polymer pens having sub-20-nm tips to perform chemical lift-off lithography (CLL). As such, we developed a hybrid patterning strategy called polymer-pen chemical lift-off lithography (PPCLL). We demonstrated PPCLL patterning using pyramidal and v shaped polymer-pen arrays. Associated simulations revealed a nanometer-scale quadratic relationship between contact linewidths of the polymer pens and two other variables: polymer-pen base linewidths and vertical compression distances...
April 14, 2017: Nano Letters
https://www.readbyqxmd.com/read/28408842/spotlight-on-ibrutinib-and-its-potential-in-frontline-treatment-of-chronic-lymphocytic-leukemia
#15
REVIEW
Maliha Khan, Jamie L Gibbons, Alessandra Ferrajoli
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the adult population. Current efforts are focused on better understanding the intricate pathophysiology of the disease to develop successful targeted therapies. Ibrutinib is emerging as an important agent in this new age of targeted treatment for CLL. As a Bruton's tyrosine kinase inhibitor, it blocks the signaling pathway that malignant B-lymphocytes need for growth and maturation. Ibrutinib's role in therapy was further expanded recently when the US Food and Drug Administration approved its use in both frontline and salvage treatment for patients with CLL...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28408436/cyclin-d1-overexpression-in-proliferation-centres-of-small-lymphocytic-lymphoma-chronic-lymphocytic-leukaemia
#16
Larissa Sena Teixeira Mendes, Natalie Peters, Ayoma D Attygalle, Andrew Wotherspoon
The recent publication reviewing the updated WHO classification commented on the presence of cyclin D1-positive cells in the proliferation centres (PC) of small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL). The figure quoted was 30%, which appeared higher than our experience. To assess cyclin D1 expression in PC of SLL/CLL cases, we performed a review of SLL/CLL cases diagnosed at the Royal Marsden Hospital between 1996 and 2009. Of 105 SLL/CLL cases, 16.2% showed expression of cyclin D1 in PC with none carrying the translocation t(11;14)(q13;q32)...
April 13, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28407516/quantitative-mir-analysis-in-chronic-lymphocytic-leukaemia-small-lymphocytic-lymphoma-proliferation-centres-are-characterized-by-high-mir-92a-and-mir-155-and-low-mir-150-expression
#17
Kinga Szurián, Irén Csala, Violetta Piurkó, Linda Deák, András Matolcsy, Lilla Reiniger
Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal abnormalities have already been described to accumulate preferably in the PCs as opposed to the intervening small cell areas. To further characterize the pathogenic role of PCs, the expression levels of 17 selected miRs known to be involved in the development of CLL/SLL were compared in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL...
April 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28402581/akt-inhibitor-mk-2206-in-combination-with-bendamustine-and-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukemia-results-from-the-n1087-alliance-study
#18
Jeremy T Larsen, Tait D Shanafelt, Jose F Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee Tschumper, Diane Jelinek, Neil E Kay, Wei Ding
Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6...
April 12, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28399885/next-generation-sequencing-and-fish-studies-reveal-the-appearance-of-gene-mutations-and-chromosomal-abnormalities-in-hematopoietic-progenitors-in-chronic-lymphocytic-leukemia
#19
Miguel Quijada-Álamo, María Hernández-Sánchez, Cristina Robledo, Jesús-María Hernández-Sánchez, Rocío Benito, Adrián Montaño, Ana E Rodríguez-Vicente, Dalia Quwaider, Ana-África Martín, María García-Álvarez, María Jesús Vidal-Manceñido, Gonzalo Ferrer-Garrido, María-Pilar Delgado-Beltrán, Josefina Galende, Juan-Nicolás Rodríguez, Guillermo Martín-Núñez, José-María Alonso, Alfonso García de Coca, José A Queizán, Magdalena Sierra, Carlos Aguilar, Alexander Kohlmann, José-Ángel Hernández, Marcos González, Jesús-María Hernández-Rivas
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as a mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, the presence of both chromosomal aberrations and gene mutations in CD34+ cells from the same patients has not been explored. METHODS: Amplicon-based deep next-generation sequencing (NGS) studies were carried out in magnetically activated-cell-sorting separated CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1 genes...
April 11, 2017: Journal of Hematology & Oncology
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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