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https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#1
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#2
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#3
Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29315094/cd19-chimeric-antigen-receptor-t-cells-from-patients-with-chronic-lymphocytic-leukemia-display-an-elevated-ifn-%C3%AE-production-profile
#4
Isabelle Magalhaes, Ingrid Kalland, James N Kochenderfer, Anders Österborg, Michael Uhlin, Jonas Mattsson
CD19 chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated dramatic results for the treatment of B cell malignancies such as chronic lymphocytic leukemia (CLL). As T cell defects are common in patients with CLL, we compared the T cells from these patients with healthy donors (HDs), and subsequently the CD19 CAR T cells produced from patients and HDs. Despite initial differences when comparing the phenotype of circulating T cells in patients with CLL and HDs, the CD19 CAR T cells manufactured from patients' or HDs' cells showed a similar phenotype (effector memory or terminally differentiated), both were specifically activated by and killed CD19 target cells, and secreted cytokines (ie, IL-2, TNF, and IFN-γ)...
January 8, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29299750/elevated-absolute-nk-cell-counts-in-peripheral-blood-predict-good-prognosis-in-chronic-lymphocytic-leukemia
#5
Wen-Ting Wang, Hua-Yuan Zhu, Yu-Jie Wu, Yi Xia, Jia-Zhu Wu, Wei Wu, Jin-Hua Liang, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu
PURPOSE: The aim of this study was to investigate the prognostic significance of the absolute natural killer (NK) cell counts in peripheral blood in patients with chronic lymphocytic leukemia (CLL). METHODS: A total of 273 previously untreated patients with CLL from April 2004 and October 2015 were enrolled into this retrospective study. We analysed the T cell subsets of all patients and figured out the number of NK cells. Comparisons of NK cell count as continuous parameter in different groups were described using Mann-Whitney U test and the Kruskal-Wallis test...
January 3, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29296862/brafv600e-accelerates-disease-progression-and-enhances-immune-suppression-in-a-mouse-model-of-b-cell-leukemia
#6
Yo-Ting Tsai, Aparna Lakshmanan, Amy Lehman, Bonnie K Harrington, Fabienne McClanahan Lucas, Minh Tran, Ellen J Sass, Meixiao Long, Alan D Flechtner, Florinda Jaynes, Krista La Perle, Vincenzo Coppola, Gerard Lozanski, Natarajan Muthusamy, John C Byrd, Michael R Grever, David M Lucas
Mutated mitogen-activated protein kinase (MAPK) pathway components promote tumor survival, proliferation, and immune evasion in solid tumors. MAPK mutations occur in hematologic cancers as well, but their role is less clear and few models are available to study this. We developed an in vivo model of disseminated BRAFV600E B-cell leukemia to determine the effects of this mutation on tumor development and immune evasion. Mice with B-cell-restricted BRAFV600E expression crossed with the Eµ-TCL1 model of chronic lymphocytic leukemia (CLL) developed leukemia significantly earlier (median, 4...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296833/emerging-role-of-bcr-signaling-inhibitors-in-immunomodulation-of-chronic-lymphocytic-leukemia
#7
REVIEW
Kamira Maharaj, Eva Sahakian, Javier Pinilla-Ibarz
Approved therapies that target the B-cell receptor (BCR) signaling pathway, such as ibrutinib and idelalisib, are known to show activity in chronic lymphocytic leukemia (CLL) via their direct effects on crucial survival pathways in malignant B cells. However, these therapies also have effects on T cells in CLL by mediating toxicity and possibly controlling disease. By focusing on the effects of BCR signaling inhibitors on the T-cell compartment, we may gain new insights into the comprehensive biological outcomes of systemic treatment to further understand mechanisms of drug efficacy, predict the toxicity or adverse events, and identify novel combinatorial therapies...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296799/near-tetraploidy-is-associated-with-richter-transformation-in-chronic-lymphocytic-leukemia-patients-receiving-ibrutinib
#8
Cecelia R Miller, Amy S Ruppert, Nyla A Heerema, Kami J Maddocks, Jadwiga Labanowska, Heather Breidenbach, Gerard Lozanski, Weiqiang Zhao, Amber L Gordon, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Leslie A Andritsos, Kristie A Blum, Farrukh T Awan, Kerry A Rogers, Michael R Grever, Amy J Johnson, Lynne V Abruzzo, Erin K Hertlein, James S Blachly, Jennifer A Woyach, John C Byrd
Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295645/favorable-immune-signature-in-cll-patients-defined-by-antigen-specific-t-cell-responses-might-prevent-second-skin-cancers
#9
Juliane Sarah Walz, Daniel Johannes Kowalewski, Linus Backert, Annika Nelde, Oliver Kohlbacher, Benjamin Weide, Lothar Kanz, Helmut Rainer Salih, Hans-Georg Rammensee, Stefan Stevanović
The course of chronic lymphocytic leukemia (CLL), inducing an immunosuppressed state that also affects T cells as central components of adaptive immunity, predisposes patients to develop second malignancies with skin cancer being the most common. Recently, we found that prevalence of memory T cells with specificity for CLL-associated antigens defined by mass spectrometry-based immunopeptidome analysis correlated with a significant survival benefit. Here, we analyzed our CLL patient cohort for second skin (pre)malignancies and found a significantly lower incidence of skin cancer in the patients showing immune responses to CLL-associated antigens...
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29286619/comparison-of-diagnostic-yield-of-a-fish-panel-against-conventional-cytogenetic-studies-for-hematological-malignancies-a-south-indian-referral-laboratory-analysis-of-201-cases
#10
Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S
Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29284783/cd150-and-cd180-are-involved-in-regulation-of-transcription-factors-expression-in-chronic-lymphocytic-leukemia-cells
#11
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29284776/the-tgf-beta%C3%A2-smad-pathway-is-inactivated-in%C3%A2-cronic%C3%A2-lymphocytic-leukemia-cells
#12
A Matveeva, L Kovalevska, I Kholodnyuk, T Ivanivskaya, E Kashuba
AIM: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. OBJECTS AND METHODS: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of transcription factors using RT2 profiler assay, bioinformatics analysis of publicly available data bases on expression. RESULTS: We have shown that the TGFB - SMAD canonical pathway is not active in CLL cells...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29277764/distribution-of-curcumin-and-thc-in-peripheral-blood-mononuclear-cells-isolated-from-healthy-individuals-and-patients-with-chronic-lymphocytic-leukemia
#13
Gordon T Bolger, Albert Licollari, Aimin Tan, Richard Greil, Lisa Pleyer, Brigitta Vcelar, Muhammad Majeed, Peter Sordillo
Background/Aim: Curcumin is being widely investigated for its anticancer properties and studies in the literature suggest that curcumin distributes to a higher degree in tumor versus non-tumor cells. In the current study, we report on investigation of the distribution of curcumin and metabolism to THC in PBMC from healthy individuals and chronic lymphocytic leukemia (CLL) patients following exposure to Lipocurc™ (liposomal curcumin). Materials and Methods: The time and temperature-dependent distribution of liposomal curcumin and metabolism to tetrahydrocurcumin (THC) were measured in vitro in human peripheral blood mononuclear cells (PBMC) obtained from healthy individuals, PBMCHI(cryopreserved and freshly isolated PBMC) and CLL patients (cryopreserved PBMC) with lymphocyte counts ranging from 17-58×106 cells/ml (PBMCCLL,Grp 1) and >150×106 cells/ml (PBMCCLL,Grp 2)...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29276179/cd4-t-cells-are-exhausted-and-show-functional-defects-in-chronic-lymphocytic-leukemia
#14
Esmaeil Allahmoradi, Saeid Taghiloo, Mohsen Tehrani, Hadi Hossein-Nattaj, Ghasem Janbabaei, Ramin Shekarriz, Hossein Asgarian-Omran
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become "exhausted" and characterized with poor effector functions and the expression of multiple inhibitory receptors. OBJECTIVE: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29246942/synergistic-targeting-of-the-regulatory-and-catalytic-subunits-of-pi3k%C3%AE-in-mature-b-cell-malignancies
#15
Jeffrey Cooney, An-Ping Lin, Daifeng Jiang, Long Wang, Avvaru N Suhasini, Jamie Myers, ZhiJun Qiu, Albert Wölfler, Heinz Sill, Ricardo C T Aguiar
PURPOSE: Aberrant activation of the B cell receptor (BCR) is implicated in the pathogenesis of mature B-cell tumors, a concept validated in part by the clinical success of inhibitors of the BCR-related kinases BTK (Bruton's tyrosine kinase) and PI3Kδ (Phosphatidylinositol-4,5-bisphosphate 3-kinase delta). These inhibitors have limitations, including the paucity of complete responses, acquired resistance, and toxicity. Here we examined the mechanism by which the cyclic-AMP/PDE4 signaling axis suppresses PI3K, towards identifying a novel mechanism-based combinatorial strategy to attack BCR-dependency in mature B-cell malignancies...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29207878/cd20-cd19-bispecific-car-t-cells-for-the-treatment-of-b-cell-malignancies
#16
Alexandra Martyniszyn, Ann-Christin Krahl, Maya C André, Andreas A Hombach, Hinrich Abken
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells which lack the CAR targeted antigen. In this situation a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing also leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T cell activation...
December 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29196709/lck-is-a-relevant-target-in-chronic-lymphocytic-leukaemia-cells-whose-expression-variance-is-unrelated-to-disease-outcome
#17
Kathleen J Till, John C Allen, Fatima Talab, Ke Lin, David Allsup, Lynn Cawkwell, Alison Bentley, Ingo Ringshausen, Andrew D Duckworth, Andrew R Pettitt, Nagesh Kalakonda, Joseph R Slupsky
Pathogenesis of chronic lymphocytic leukaemia (CLL) is contingent upon antigen receptor (BCR) expressed by malignant cells of this disease. Studies on somatic hypermutation of the antigen binding region, receptor expression levels and signal capacity have all linked BCR on CLL cells to disease prognosis. Our previous work showed that the src-family kinase Lck is a targetable mediator of BCR signalling in CLL cells, and that variance in Lck expression associated with ability of BCR to induce signal upon engagement...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196338/proteomics-and-metabolomics-identify-molecular-mechanisms-of-aging-potentially-predisposing-for-chronic-lymphocytic-leukemia
#18
Rupert Laurenz Mayer, Josef D Schwarzmeier, Marlene C Gerner, Andrea Bileck, Johanna C Mader, Samuel M Meier-Menches, Samuel M Gerner, Klaus G Schmetterer, Tobias Pukrop, Albrecht Reichle, Astrid Slany, Christopher Gerner
B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, also the chronic B cell leukemia cell line JVM-13 was included. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells...
December 1, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29194473/esmo-consensus-conference-on-malignant-lymphoma-general-perspectives-and-recommendations-for-the-clinical-management-of-the-elderly-patient-with-malignant-lymphoma
#19
C Buske, M Hutchings, M Ladetto, V Goede, U Mey, P Soubeyran, M Spina, R Stauder, M Trnený, U Wedding, P Fields
The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (1) the elderly patient, (2) prognostic factors suitable for clinical use, and (3) the 'ultra-high-risk' group...
November 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29193006/a-single-institution-retrospective-cohort-study-of-first-line-r-epoch-chemoimmunotherapy-for-richter-syndrome-demonstrating-complex-chronic-lymphocytic-leukaemia-karyotype-as-an-adverse-prognostic-factor
#20
Kerry A Rogers, Ying Huang, Amy S Ruppert, Galena Salem, Deborah M Stephens, Nyla A Heerema, Leslie A Andritsos, Farrukh T Awan, John C Byrd, Joseph M Flynn, Kami J Maddocks, Jeffrey A Jones
Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014...
November 28, 2017: British Journal of Haematology
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