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CLL, chronic lymphocytic leukemia

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https://www.readbyqxmd.com/read/29791237/the-future-of-chronic-lymphocytic-leukemia-potential-directions-from-ash-2017
#1
Stefano Molica
Novel targeted therapies - including ibrutinib, venetoclax and idelalisib - have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). Therefore, studying combinations of novel agents (NAs) with distinct mechanism of action and non-overlapping toxicities is challenging. Area covered: The 2017 American Society Hematology (ASH) Annual Meeting, has represented a showcase for several trials combining NAs. These studies are currently evaluating the efficacy NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody) and NA plus chemo-immunotherapy...
May 23, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29787919/optimal-use-of-novel-agents-in-chronic-lymphocytic-leukemia
#2
Mitchell R Smith, Robert F Weiss
Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse...
May 7, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29787597/asymmetric-and-symmetric-dimethylarginines-and-mortality-in-patients-with-hematological-malignancies-a-prospective-study
#3
Angelika Chachaj, Jerzy Wiśniewski, Justyna Rybka, Aleksandra Butrym, Monika Biedroń, Małgorzata Krzystek-Korpacka, Mariusz Grzegorz Fleszar, Maciej Karczewski, Tomasz Wróbel, Grzegorz Mazur, Andrzej Gamian, Andrzej Szuba
The study was designed to determine the associations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines plasma concentrations with all-cause mortality in patients with hematological malignancies. 33 patients with acute myeloid leukemia (AML), 31 patients with non-Hodgkin's lymphoma (nHL), 32 patients with chronic lymphocytic leukemia (CLL) and 48 patients without malignancy were enrolled into the study. Each patient was followed until death or for at least 14.5 months (range: 14.5-53). Median ADMA and SDMA were significantly elevated in AML, nHL and CLL compared to controls (ADMA: 1...
2018: PloS One
https://www.readbyqxmd.com/read/29785028/the-reference-epigenome-and-regulatory-chromatin-landscape-of-chronic-lymphocytic-leukemia
#4
Renée Beekman, Vicente Chapaprieta, Núria Russiñol, Roser Vilarrasa-Blasi, Núria Verdaguer-Dot, Joost H A Martens, Martí Duran-Ferrer, Marta Kulis, François Serra, Biola M Javierre, Steven W Wingett, Guillem Clot, Ana C Queirós, Giancarlo Castellano, Julie Blanc, Marta Gut, Angelika Merkel, Simon Heath, Anna Vlasova, Sebastian Ullrich, Emilio Palumbo, Anna Enjuanes, David Martín-García, Sílvia Beà, Magda Pinyol, Marta Aymerich, Romina Royo, Montserrat Puiggros, David Torrents, Avik Datta, Ernesto Lowy, Myrto Kostadima, Maša Roller, Laura Clarke, Paul Flicek, Xabier Agirre, Felipe Prosper, Tycho Baumann, Julio Delgado, Armando López-Guillermo, Peter Fraser, Marie-Laure Yaspo, Roderic Guigó, Reiner Siebert, Marc A Martí-Renom, Xose S Puente, Carlos López-Otín, Ivo Gut, Hendrik G Stunnenberg, Elias Campo, Jose I Martin-Subero
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#5
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29781039/sex-dependent-association-of-circulating-sex-steroids-and-pituitary-hormones-with-treatment-free-survival-in-chronic-lymphocytic-leukemia-patients
#6
Eric P Allain, Karin Venzl, Patrick Caron, Véronique Turcotte, David Simonyan, Michaela Gruber, Trang Le, Eric Lévesque, Chantal Guillemette, Katrina Vanura
Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic influence on treatment-free survival (TFS). In 156 CLL cases, we quantitatively profiled 29 circulating steroids (progesterone, adrenal precursors, androgens, estrogens, and catechol estrogens) as well as luteinizing hormone (LH) and follicle-stimulating hormone...
May 21, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29779348/-prognostic-significance-of-cll-ipi-for-chinese-patients-with-chronic-lymphocytic-leukemia
#7
H Y Zhu, L Wang, J Qiao, Y X Zou, Y Xia, W Wu, L Cao, J H Liang, L Fan, W Xu, J Y Li
Objective: To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients. Methods: Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system. Results: ①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779347/-clinical-analysis-of-70-chronic-lymphocytic-leukemia-patients-with-trisomy-12-detected-by-fish
#8
R Lyu, Z J Li, H Li, S H Yi, W Liu, T Y Wang, W J Xiong, L G Qiu
Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases). Results: Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#9
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29765537/stat3-activated-cd36-facilitates-fatty-acid-uptake-in-chronic-lymphocytic-leukemia-cells
#10
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764250/immunological-changes-with-kinase-inhibitor-therapy-for-chronic-lymphocytic-leukemia
#11
Christopher Pleyer, Adrian Wiestner, Clare Sun
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib...
May 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29763855/identification-of-new-phosphorylation-sites-of-cd23-in-b-cells-of-patients-with-chronic-lymphocytic-leukemia
#12
Martina Maďarová, Rastislav Mucha, Stanislav Hresko, Zuzana Makarová, Zuzana Gdovinová, Jarmila Szilasiová, Marianna Vitková, Tomáš Guman, Natalia Štecová, Tomas Dobransky
B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease. Here we report changes in the phosphorylation of CD23 on threonine (pThr314) and two serine residues (pSer254, pSer265) in B lymphocytes of B-CLL patients, using a flow cytometry approach...
May 9, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#13
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29761374/the-prognostic-role-of-hbv-infection-in-chronic-lymphocytic-leukemia
#14
Jin-Hua Liang, Rui Gao, Jun-Cheng Dai, Robert Peter Gale, Wang Li, Lei Fan, Zhi-Bin Hu, Wei Xu, Jian-Yong Li
PURPOSE: We attempt to assess the impact of hepatis-B virus (HBV) status on the prognosis of chronic lymphocytic leukemia (CLL) using a Chinese case cohort. METHODS: Five hundred and one consecutive newly diagnosed subjects with CLL were enrolled in this case cohort. HBV infection was defined as hepatitis B surface antigen (HBsAg) positive or hepatitis-B core antibody (HBcAb) positive. Univariate and stepwise multivariate Cox regression analyses were used to screen the prognostic risk factors associated with the end point of time-to-treatment (TTT) or overall survival (OS)...
May 14, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29760835/cutaneous-mucormycosis-following-a-bullous-pemphigoid-flare-in-a-chronic-lymphocytic-leukemia-patient-on-ibrutinib
#15
Matthew K Stein, Saradasri Karri, Jackson Reynolds, Jeff Owsley, Austin Wise, Mike G Martin, Fereshteh Zare
While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#16
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29757455/cells-cytokines-chemokines-and-cancer-stress-a-biobehavioral-study-of-patients-with-chronic-lymphocytic-leukemia
#17
Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
https://www.readbyqxmd.com/read/29756258/a-prospective-analysis-of-circulating-saturated-and-monounsaturated-fatty-acids-and-risk-of-non-hodgkin-lymphoma
#18
Yu-Han Chiu, Kimberly A Bertrand, Shumin Zhang, Francine Laden, Mara M Epstein, Bernard A Rosner, Stephanie Chiuve, Hannia Campos, Edward L Giovannucci, Jorge E Chavarro, Brenda M Birmann
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752258/how-and-when-i-do-allogeneic-transplant-in-cll
#19
John G Gribben
Allogenic stem cell transplantation (allo-SCT) has been considered the treatment of choice for high-risk patients with chronic lymphocytic leukemia (CLL) and the only approach offered with curative intent in this disease. The availability novel agents including the B cell receptor inhibitors (BCRi) ibrutinib, acalabrutinib and idelalisib, as well as venetoclax which targets the BCL2 pathway and the success of these agents in treating high-risk disease patients has made it more difficult to assess who and when in their treatment course allo-SCT should be considered...
May 11, 2018: Blood
https://www.readbyqxmd.com/read/29750316/elevated-soluble-cd23-level-indicates-increased-risk-of-b-cell-non-hodgkin-s-lymphomas-evidence-from-a-meta-analysis
#20
REVIEW
Yi-Shu Huang, Xiang Zhou, Zhi-Fang Yang, Zheng-Tao Lv
The aim of the present study was to determine whether circulating soluble CD23 (sCD23) was associated with B cells non-Hodgkin's lymphomas (B-NHL). PubMed, EMBASE, and ISI Web of Science were extensively searched without language restriction. Data was extracted in a standardized data collection sheet after two reviewers scanned studies independently. The association between sCD23 and NHL was indicated as odds ratio (OR) along with its related 95% confidence interval (95% CI). Meta-analysis was conducted via RevMan 5...
May 11, 2018: Annals of Hematology
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