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CLL, chronic lymphocytic leukemia

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https://www.readbyqxmd.com/read/28811973/nk-cell-dysfunction-in-chronic-lymphocytic-leukemia-is-associated-with-loss-of-the-mature-cells-expressing-inhibitory-killer-cell-ig-like-receptors
#1
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810332/-study-on-the-expression-of-trip13-mrna-in-chronic-lymphocytic-leukemia-b-lymphocyte-and-the-molecular-mechanism-of-trip13-mediated-jvm-2-cell-proliferation-and-apoptosis
#2
K S Zhou, Q Zhang, W T Zhang, Y Y Liu, S S Wu, J Zhou, X D Wei, Y P Song
Objective: To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) . Methods: Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19(+) B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#3
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#4
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28802891/time-to-second-line-treatment-and-subsequent-relative-survival-in-older-patients-with-relapsed-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#5
Eric M Ammann, Tait D Shanafelt, Melissa C Larson, Kara B Wright, Bradley D McDowell, Brian K Link, Elizabeth A Chrischilles
BACKGROUND: Novel targeted therapies offer excellent short-term outcomes in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). However, there is disagreement over how widely these therapies should be used in place of standard chemo-immunotherapy (CIT). We investigated whether stratification on the length of the interval between first-line (T1) and second-line (T2) treatments could identify a subgroup of older patients with relapsed CLL/SLL with an expectation of normal overall survival, and for whom CIT could be an acceptable treatment choice...
July 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28797620/extended-follow-up-of-patients-treated-with-bendamustine-for-lymphoid-malignancies
#6
Mara Penne, Maryam Sarraf Yazdy, Kruti Sheth Nair, Bruce D Cheson
INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28791248/an-unusual-presentation-of-chronic-lymphocytic-leukemia
#7
Dinesh Atwal, Mihir Raval, Belal Firwana, Jeanette Ramos, Appalanaidu Sasapu
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a B-cell lymphocytic neoplasm with indolent clinical course. If identified early, observation is opted. Many variables lead to the initiation of treatment. Authors describe a 62-year-old male presenting with shortness of breath and found to have white cell count of 1360 × 10(9)/L and subsequently was diagnosed with CLL/SLL. The patient received leukapheresis along with tumor lysis treatment and systemic chemotherapy with fludarabine, cyclophosphamide, and rituximab regimen...
July 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#8
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28783166/anti-leukemic-activity-of-microrna-26a-in-a-chronic-lymphocytic-leukemia-mouse-model
#9
L D'Abundo, E Callegari, A Bresin, A Chillemi, B K Elamin, P Guerriero, X Huang, E Saccenti, E M A A Hussein, F Casciano, P Secchiero, G Zauli, G A Calin, G Russo, L J Lee, C M Croce, G Marcucci, S Sabbioni, F Malavasi, M Negrini
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eμ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#10
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#11
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28776453/new-drug-discovery-approaches-targeting-recurrent-mutations-in-chronic-lymphocytic-leukemia
#12
Rupal Tripathi, Eriong Lee-Verges, Morihiro Higashi, Neus Gimenez, Laia Rosich, Monica Lopez-Guerra, Dolors Colomer
Next generation sequencing has provided a comprehensive understanding of the mutational landscape in chronic lymphocytic leukemia (CLL), and new drivers have been identified. Some of these drivers could be pharmacologically targeted to choose the most effective personalized therapy in each CLL patient. Areas covered: In this article, the authors uncover the potential role of new targeted therapies against the most recurrent mutations in CLL as well as the recently approved therapies. The authors also provide their expert opinion and give their perspectives for the future...
August 4, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28767449/sf3b1-mutation-is-a-prognostic-factor-in-chronic-lymphocytic-leukemia-a-meta-analysis
#13
Zhenghao Zhang, Shu Chen, Shuang Chen, Gang Chen, Rui Zhang, Jinhua Li, Jianhua Qu
Recent studies suggest that SF3B1 might be related to poor prognosis in CLL, but the results remain controversial. This meta-analysis was performed to clarify the relationship between SF3B1 mutation and prognosis in patients with CLL. The relevant published reports were searched in PubMed, EMBASE, and Web of Science. A total of 13 articles were included in this meta-analysis as they met the inclusion and exclusion criteria. The hazard ratios (HRs) and corresponding 95% confidence intervals (95%CIs) for progression free survival (PFS) and/or overall survival (OS) were extracted from each eligible study...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766542/-efficacy-of-a-bendamustine-and-rituximab-combination-in-first-line-therapy-for-chronic-lymphocytic-leukemia-results-of-the-ben-001-study
#14
E A Stadnik, V V Strugov, T O Andreeva, Yu V Virts, A M Rumyantsev, Yu V Mirolyubova, P A Butylin, A Yu Zaritsky
AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28766389/pharmacokinetics-efficacy-and-safety-of-the-rituximab-biosimilar-ct-p10
#15
Bertrand Coiffier
Rituximab, an anti-CD20 monoclonal antibody, is a key therapeutic in the treatment of B cell lymphomas and rheumatoid arthritis (RA). Global rates of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and RA are increasing, with a concomitant rise in individual and overall treatment costs. As such, biosimilar development may help facilitate greater access to treatment. The rituximab biosimilar CT-P10 (Truxima®) has recently received approval in Europe and South Korea for all indications held by reference rituximab (RTX)...
August 2, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28762636/blockage-of-wnt-%C3%AE-catenin-signaling-by-nanoparticles-reduces-survival-and-proliferation-of-cll-cells-in-vitro-preliminary-study
#16
Ida Franiak-Pietryga, Henryk Maciejewski, Barbara Ziemba, Dietmar Appelhans, Brigitte Voit, Tadeusz Robak, Magdalena Jander, Jacek Treliński, Maria Bryszewska, Maciej Borowiec
The Wnt/β-catenin signaling pathway is shown to play a significant role in the control of the survival, proliferation, and differentiation of hematopoietic cells. Studies have confirmed that aberrant activation of canonical Wnt signaling occurs in various forms of leukemia, and is crucial for chronic lymphocytic leukemia (CLL) pathogenesis. The aim of the study is to evaluate the influence of maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers (PPI-G4) on Wnt/β-catenin pathway gene expression in CLL (MEC-1) cells and to compare these findings with those obtained with fludarabine (FA)...
August 1, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#17
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
July 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28758262/paraneoplastic-pemphigus-seen-in-4-patients-with-hematologic-malignancies-formerly-treated-with-rituximab
#18
C Baykal, S Kılıç, R Küçükoğlu
Paraneoplastic pemphigus (PNP) is a peculiar variant of pemphigus with pathognomonic clinical, histological, and immunological features. It is typically associated with hematologic malignancies (84%), such as non-Hodgkin lymphomas (NHL) (most common), chronic lymphocytic leukemia (CLL), Castleman disease, thymoma, Waldenström's macroglobulinemia, Hodgkin lymphoma, and monoclonal gammopathy, as well as non-hematological neoplasms, such as epithelial carcinomas, mesenchymal sarcomas, and malignant melanoma. This article is protected by copyright...
July 31, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28755313/targeting-b-cell-signaling-in-chronic-lymphocytic-leukemia
#19
REVIEW
Jon E Arnason, Jennifer R Brown
In recent years, a revolution in the management of chronic lymphocytic leukemia (CLL) has centered on the targeting of the B cell receptor (BCR) signaling pathway. Our improved understanding of the biology of cell signaling in CLL and the development of oral kinase inhibitors directed at the BCR pathway has led to the approval of two new agents and has the potential to radically change the treatment of CLL in both the relapsed/refractory and upfront settings. In this review, we will describe the underlying biology of the BCR signaling pathway...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#20
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
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