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https://www.readbyqxmd.com/read/29136511/snapshot-chronic-lymphocytic-leukemia
#1
Elisa Ten Hacken, Romain Guièze, Catherine J Wu
Despite the recent advances in the therapeutic management of Chronic Lymphocytic Leukemia (CLL) patients, this common B cell malignancy still remains incurable. This SnapShot provides an overview of CLL biology and therapy, with a focus on genetics and microenvironmental interactions, which contribute to disease progression and therapy resistance. To view this SnapShot, open or download the PDF.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#2
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29129824/impact-of-fish-aberrations-and-cllu1-expression-on-the-prognosis-of-chronic-lymphocytic-leukemia-presentation-of-156-patients-from-turkey
#3
Ümmet Abur, Gönül Oğur, Ömer Salih Akar, Engin Altundağ, Huri Sema Aymelek, Düzgün Özatlı, Mehmet Turgut
OBJECTIVE: This study evaluates the impact of the CLLU1 expression and FISH analysis of a group of Turkish CLL patients. MATERIALS AND METHODS: Totally, 156 CLL patients were analysed by FISH method;47 of them were also evaluated for CLLU1 expression. Results were correlated with clinical parameters. RESULTS: FISH aberrations were found in 62% of patients. These aberrations were del13q14 (67%), trisomy 12 (27%), del11q22 (19%), del17p (8%) and 14q32 rearrangements (20%)...
November 13, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29125406/bruton-s-tyrosine-kinase-inhibitors-first-and-second-generation-agents-for-patients-with-chronic-lymphocytic-leukemia-cll
#4
Philip A Thompson, Jan A Burger
The BTK inhibitor ibrutinib is effective in both low- and high-risk CLL patients, achieving durable remissions with continuous therapy in the majority of patients. Ibrutinib lacks myelotoxicity and is generally well tolerated by older and unfit patients; however, side effects, such as atrial fibrillation or hemorrhage, can result in treatment interruption or discontinuation. Given the high efficacy and overall safety, ibrutinib is increasingly used in untreated and previously treated CLL patients. Second-generation BTK inhibitors are being developed, with different and generally more BTK-selective kinase inhibition profiles, which may increase the safety and/or efficacy...
November 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29125235/comparison-of-the-mrna-expression-profile-of-b-cell-receptor-components-in-normal-cd5-high-b-lymphocytes-and-chronic-lymphocytic-leukemia-a-key-role-of-zap70
#5
Aleena A Gladkikh, Daria M Potashnikova, Victor Tatarskiy, Margarita Yastrebova, Alvina Khamidullina, Natasha Barteneva, Ivan Vorobjev
The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29123965/ig-like-transcript-2-ilt2-suppresses-t-cell-function-in-chronic-lymphocytic-leukemia
#6
Mónica Villa-Álvarez, Seila Lorenzo-Herrero, Ana P Gonzalez-Rodriguez, Alejandro López-Soto, Angel R Payer, Esther Gonzalez-Garcia, Leticia Huergo-Zapico, Segundo Gonzalez
Chronic lymphocytic leukemia (CLL) is associated with a profound dysregulation of the immune system. Loss of T cell function is frequently caused in cancer by sustained signaling of inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2) in the pathogenesis of CLL. We observed that ILT2 expression was markedly reduced on leukemic cells, whereas it was increased on CD8 and CD4 T cells from CLL patients, particularly in those patients harboring chromosome 11q deletion, which includes the ATM gene...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#7
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29115892/management-of-patients-with-chronic-lymphocytic-leukemia-at-high-risk-of-relapse-on-ibrutinib-therapy
#8
Ayed O Ayed, Sameer A Parikh
The past two decades have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL), particularly with the introduction of targeted therapies to clinical practice. Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has shown significant efficacy and tolerability, even in heavily treated patients. Despite improvement in outcomes, patients do ultimately relapse. Those who develop disease progression on ibrutinib are a particularly high-risk population with poor outcomes...
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29115891/the-mutational-landscape-of-small-lymphocytic-lymphoma-compared-to-non-early-stage-chronic-lymphocytic-leukemia
#9
Alejandra Martínez-Trillos, Magda Pinyol, Julio Delgado, Marta Aymerich, Maria Rozman, Tycho Baumann, Marcos González-Díaz, Jesus M Hernández, Miguel Alcoceba, Anna Muntañola, Maria José Terol, Blanca Navarro, Eva Giné, Pedro Jares, Sílvia Beà, Alba Navarro, Dolors Colomer, Ferran Nadeu, Enrique Colado, Angel R Payer, Tomás García-Cerecedo, Xosé S Puente, Carlos López-Otin, Elias Campo, Armando López-Guillermo, Neus Villamor
Small lymphocytic lymphoma (SLL) is considered as the non-leukemic form of presentation of chronic lymphocytic leukemia (CLL). We have compared the features, genomic alterations, and outcome of 890 patients with CLL and SLL. One hundred and thirteen patients presented as SLL and more frequently had unmutated-IGHV, CD38(high), ZAP-70(high), CD49d(high), +12, alterations in genes of NOTCH1, cell cycle, RNA metabolism, and NFkB pathways than CLL. During the follow-up, 46% of SLL patients developed CLL. Time to first treatment (TTFT) was shorter in SLL (10-year: 75% vs 62%; p = ...
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29100411/gene-body-hypermethylation-controlled-cryptic-promoter-and-mir26a1-dependent-ezh2-regulation-of-tet1-gene-activity-in-chronic-lymphocytic-leukemia
#10
Pradeep Kumar Kopparapu, Mohammad Hamdy Abdelrazak Morsy, Chandrasekhar Kanduri, Meena Kanduri
The Ten-eleven-translocation 1 (TET1) protein is a member of dioxygenase protein family that catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. TET1 is differentially expressed in many cancers, including leukemia. However, very little is known about mechanism behind TET1 deregulation. Previously, by characterizing global methylation patterns in CLL patients using MBD-seq, we found TET1 as one of the differentially methylated regions with gene-body hypermethylation. Herein, we characterize mechanisms that control TET1 gene activity at the transcriptional level...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099493/pharmacodynamics-and-proteomic-analysis-of-acalabrutinib-therapy-similarity-of-on-target-effects-to-ibrutinib-and-rationale-for-combination-therapy
#11
V K Patel, B Lamothe, M L Ayres, J Gay, J Cheung, K Balakrishnan, C Ivan, J Morse, M Nelson, M J Keating, W G Wierda, J R Marszalek, V Gandhi
Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL), however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation, and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29097160/clinical-practice-guidelines-for-diagnosis-and-treatment-of-chronic-lymphocytic-leukemia-cll-in-the-netherlands
#12
Sabina Kersting, Suzanne I M Neppelenbroek, Hein P J Visser, Michel van Gelder, Mark-David Levin, Rogier Mous, Ward Posthuma, Hanneke M van der Straaten, Arnon P Kater
INTRODUCTION: In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. MATERIALS AND METHODS: The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline...
September 25, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29091884/advances-in-chronic-lymphocytic-leukemia-pharmacotherapy
#13
REVIEW
Lorena Caixeta Gomes, Aline Lúcia Menezes Ferrão, Fernanda Cristina Gontijo Evangelista, Tâmara Dauare de Almeida, Rayson Carvalho Barbosa, Maria das Graças Carvalho, Adriano de Paula Sabino
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs. CLL may be indolent or aggressive and has a range of prognostic factors such as expression of CD38 and ZAP-70, immunophenotypic and cytogenetic changes, imbalanced apoptosis proteins, and others. Although CLL has a low mortality rate, this disease is generally not considered curable until today...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29082795/treatment-approach-for-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#14
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29081197/-clinical-features-and-prognosis-of-17-patients-with-primary-cold-agglutinin-disease
#15
Y Y Wu, X X Cao, H Cai, L Zhang, D B Zhou, J Li
Objective: To explore the clinical characteristics, treatment and prognosis in 17 patients with primary cold agglutinin disease (CAD) . Methods: Clinical data, treatment and survival status of 17 patients diagnosed with primary cold agglutinin disease in Peking Union Medical College Hospital during April 2007 to October 2016 were retrospectively analyzed. The MYD88(L265P) mutation was tested in 4 patients. Results: The median age of 17 patients was 67 years (range, 51-86 years) , and male- to female ratio was 1...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29080742/a-catalytically-inactive-gelatinase-b-mmp-9-mutant-impairs-homing-of-chronic-lymphocytic-leukemia-cells-by-altering-migration-regulatory-pathways
#16
Elvira Bailón, Noemí Aguilera-Montilla, Alejandra Gutiérrez-González, Estefanía Ugarte-Berzal, Philippe E Van den Steen, Ghislain Opdenakker, José A García-Marco, Angeles García-Pardo
We previously showed that MMP-9 overexpression impairs migration of primary CLL cells and MEC-1 cells transfected with MMP-9. To determine the contribution of non-proteolytic activities to this effect we generated MEC-1 transfectants stably expressing catalytically inactive MMP-9MutE (MMP-9MutE-cells). In xenograft models in mice, MMP-9MutE-cells showed impaired homing to spleen and bone marrow, compared to cells transfected with empty vector (Mock-cells). In vitro transendothelial and random migration of MMP-9MutE-cells were also reduced...
October 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29075057/evaluation-of-interleukin-9-expression-as-a-potential-therapeutic-target-in-chronic-lymphocytic-leukemia-in-a-cohort-of-egyptian-patients
#17
Hadeer A Abbassy, Reham A Aboelwafa, Omar M Ghallab
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that has a highly variable clinical course. Genomic features as zeta-chain-associated protein kinase 70 (ZAP70) expression and CD38 expression provide further differentiation of disease prognosis. Extensive studies have confirmed the oncogenic activities of IL-9 in lymphoma. The aim of the current study was to investigate the contribution of IL-9 expression to the pathogenesis of CLL and its correlation to other prognostic parameters. This study was conducted on 80 patients at diagnosis with CLL and 80 healthy controls...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29069998/composite-small-lymphocytic-lymphoma-chronic-lymphocytic-leukemia-and-follicular-lymphoma-a-clinicopathological-study-of-six-cases
#18
Fatima Zahra Jelloul, Qiang Hua Chen, Tianyu Yang, Nina Haghi, Judith Brody, Xinmin Zhang, Silvat Sheikh-Fayyaz
BACKGROUND: Composite small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and follicular lymphoma (FL) is extremely rare, and only 13 cases have been reported previously. METHODS: We identified 6 cases of composite SLL/CLL and FL in our database and studied their clinical, histologic, immunophenotypic, and cytogenetic features. A literature review of the existing cases was also conducted. RESULTS: The patients included 4 males and 2 females, with a median age of 72 years...
October 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29069762/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#19
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5(+) B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5(+)CD43(+)IgM(+)CD19(+) CLL phenotype in culture and can be adoptively transferred into Rag1(-/-) mice...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063805/telomere-length-in-poor-risk-chronic-lymphocytic-leukemia-associations-with-disease-characteristics-and-outcome
#20
Daniela Steinbrecher, Billy Michael Chelliah Jebaraj, Christof Schneider, Jennifer Edelmann, Florence Cymbalista, Véronique Leblond, Alain Delmer, Stefan Ibach, Eugen Tausch, Annika Scheffold, Johannes Bloehdorn, Michael Hallek, Peter Dreger, Hartmut Döhner, Stephan Stilgenbauer
Telomere length in chronic lymphocytic leukemia (CLL) is described as an independent prognostic factor based largely on previously untreated patients from chemotherapy based trials. Here, we studied telomere length associations in high-risk, relapsed/refractory CLL treated with alemtuzumab in the CLL2O study (n = 110) of German and French CLL study groups. Telomere length (median 3.28 kb, range 2.52-7.24 kb) was relatively short, since 84.4% of patients had 17p- which is generally associated with short telomeres...
October 24, 2017: Leukemia & Lymphoma
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