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"Chronic lymphocytic leukemia"

Mira Tout, Anne-Laure Gagez, Stéphane Leprêtre, Valérie Gouilleux-Gruart, Nicolas Azzopardi, Alain Delmer, Mélanie Mercier, Loïc Ysebaert, Kamel Laribi, Hugo Gonzalez, Gilles Paintaud, Guillaume Cartron, David Ternant
BACKGROUND AND OBJECTIVES: Rituximab is an anti-CD20 monoclonal antibody approved in the first-line treatment of patients with chronic lymphocytic leukemia (CLL). Rituximab pharmacokinetics shows a time dependency possibly related to changes in the target antigen amount over time. The purpose of this study was to quantify the influence of both CD20 antigenic mass and the FcγRIIIA genetic polymorphism on rituximab pharmacokinetics in CLL. METHODS: Rituximab pharmacokinetics was described in 118 CLL patients using a semi-mechanistic model including a latent target antigen turnover, which allowed the estimation of rituximab target-mediated elimination in addition to the endogenous clearance...
October 25, 2016: Clinical Pharmacokinetics
Ahmad Salimi, Mehryar Habibi Roudkenar, Leila Sadeghi, Alireza Mohseni, Enayatollah Seydi, Nahal Pirahmadi, Jalal Pourahmad
The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7-dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL B-lymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy B-lymphocytes and their mitochondria...
October 25, 2016: Nutrition and Cancer
Santhilal Subhash, Per-Ola Andersson, Subazini Thankaswamy Kosalai, Chandrasekhar Kanduri, Meena Kanduri
BACKGROUND: Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete genome-wide coverage. In chronic lymphocytic leukemia (CLL), the role of CpG methylated regions associated with transcribed long noncoding RNAs (lncRNA) and repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized the global methylation profile of high CpG-rich regions in different CLL prognostic subgroups based on IGHV mutational status...
2016: Clinical Epigenetics
Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
G Lohmann, E Vasyutina, J Bloehdorn, N Reinart, J I Schneider, V Babu, G Knittel, G Crispatzu, P Mayer, C Prinz, J K Muenzner, B Biersack, D G Efremov, L Chessa, C D Herling, S Stilgenbauer, M Hallek, R Schobert, H C Reinhardt, B Schumacher, M Herling
Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, but is also an increasing concern in the era of more targeted therapies. As cells with low replicative activity rely on repair that triggers checkpoint-independent non-canonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
M Larrayoz, M J J Rose-Zerilli, L Kadalayil, H Parker, S Blakemore, J Forster, Z Davis, A J Steele, A Collins, M Else, D Catovsky, D G Oscier, J C Strefford
Leukemia accepted article preview online, 24 October 2016. doi:10.1038/leu.2016.298.
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Chadi Nabhan, Anthony R Mato, Bruce A Feinberg
No abstract text is available yet for this article.
October 20, 2016: American Journal of Hematology
Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
Zoltán Mátrai, Hajnalka Andrikovics, Anikó Szilvási, András Bors, András Kozma, Emma Ádám, Gabriella Halm, Éva Karászi, Attila Tordai, Tamás Masszi
The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0...
October 18, 2016: Pathology Oncology Research: POR
Ishita Chen, Raymond B Fohtung, Hanadi Ajam Oughli, Robert Bauer, Caline Mattar, William G Powderly, Mark S Thoelke
Ramsay Hunt Syndrome (RHS) is a rare complication of latent varicella-zoster virus (VZV) infection that can occur in immunocompetent host. It usually involves ipsilateral facial paralysis, ear pain and facial vesicles. Disseminated herpes zoster is another complication of VZV infection typically seen in immunocompromised hosts. We describe a patient with relapsed chronic lymphocytic leukemia (CLL) who presented simultaneously with RHS and disseminated herpes zoster. While other complications have been documented to coexist with RHS, to our knowledge, this is the first reported case in the literature of concurrent RHS with disseminated herpes zoster...
2016: IDCases
Maulik Vyas, Ann-Charlott Schneider, Olga Shatnyeva, Katrin S Reiners, Samir Tawadros, Stephan Kloess, Ulrike Köhl, Michael Hallek, Hinrich P Hansen, Elke Pogge von Strandmann
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8(+) T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. Triplebodies in both formats showed better ability to induce NK-cell-dependent killing of target cells compared to bispecific counterparts...
2016: Oncoimmunology
Arianna Bottoni, Lara Rizzotto, Tzung-Huei Lai, Chaomei Liu, Lisa L Smith, Rose Mantel, Sean Reiff, Dalia El-Gamal, Karilyn Larkin, Amy J Johnson, Rosa Lapalombella, Amy Lehman, William Plunkett, John C Byrd, James S Blachly, Jennifer A Woyach, Deepa Sampath
BTK is a critical mediator of survival in B cell neoplasms. While BTK inhibitors have transformed therapy in CLL, high genetic risk patients are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of miRNAs that target BTK in primary CLL cells and show that the HDAC repressor complex is recruited to these miRNA promoters to silence their expression...
October 17, 2016: Blood
Kyle Crassini, Yandong Shen, Stephen Mulligan, O Giles Best
Microenvironments within the lymph node and bone marrow promote proliferation and drug resistance in chronic lymphocytic leukemia (CLL). Successful treatment of CLL must therefore target the leukemic cells within these compartments. A better understanding of the interaction between CLL cells and the tumor microenvironment has led to the development of in vitro models that mimic the mechanisms that support leukemic cell survival and proliferation in vivo. Employing these models as part of the pre-clinical evaluation of novel therapeutic agents enables a better approximation of their potential clinical efficacy...
October 18, 2016: Leukemia & Lymphoma
Neta Goldschmidt, Deborah Rund
No abstract text is available yet for this article.
October 18, 2016: Leukemia & Lymphoma
Lee Mozessohn, Craig Earle, David Spaner, Stephanie Y Cheng, Matthew Kumar, Rena Buckstein
BACKGROUND: Metabolic syndrome (MetS) is a risk factor for development of cancer. Because aberrant lipid metabolism is a pathogenic feature of chronic lymphocytic leukemia (CLL), our objective was to determine if CLL patients have a higher prevalence of MetS preceding diagnosis and to determine the impact of lipid-lowering medications on survival. METHODS: We conducted a population-based case-control study in Ontario, Canada, using administrative databases of adults age 66 years and older to compare the prevalence of MetS preceding CLL with age- and sex-matched control subjects...
March 2017: Journal of the National Cancer Institute
Ivana Milosevic
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Matthew D Seftel, John Kuruvilla, Tom Kouroukis, Versha Banerji, Graeme Fraser, Michael Crump, Rajat Kumar, Haji I Chalchal, Muhammad Salim, Rob C Laister, Susan Crocker, Spencer B Gibson, Marcia Toguchi, John F Lyons, Hao Xu, Jean Powers, Joana Sederias, Lesley Seymour, Annette E Hay
AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 with in vitro activity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m(2) twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR). Nineteen patients were accrued (7 CLL, 12 MCL). Four CLL patients achieved stable disease (SD)...
October 17, 2016: Leukemia & Lymphoma
Austin Poole, Nicole Girard, Frederic Clayton, Srinivas K Tantravahi
No abstract text is available yet for this article.
October 17, 2016: Leukemia & Lymphoma
Yali Chen, Qianxiang Zhou, Lei Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells...
October 17, 2016: Oncology Reports
Amity L Roberts, Rebecca M Davidson, Alison G Freifeld, Peter C Iwen
A case of disseminated nocardiosis caused by Nocardia arthritidis in an immunocompromised patient with a history of chronic lymphocytic leukemia and rheumatoid arthritis is presented. This report highlights the use for multilocus sequence typing (MLST) in addition to single gene molecular sequencing to identify rare Nocardia species.
2016: IDCases
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