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https://www.readbyqxmd.com/read/29672642/runx1-pdcd6-fusion-resulting-from-a-novel-t-5-21-p15-q22-chromosome-translocation-in-myelodysplastic-syndrome-secondary-to-chronic-lymphocytic-leukemia
#1
Ioannis Panagopoulos, Ludmila Gorunova, Eva-Marie Jacobsen, Kristin Andersen, Francesca Micci, Sverre Heim
Leukemic cells often carry chromosome aberrations which generate chimeric genes of pathogenetic, diagnostic, and prognostic importance. New rearrangements giving rise to novel fusion genes define hitherto unrecognized genetic leukemia subgroups. G-banding, fluorescence in situ hybridization (FISH), and molecular genetic analyses were done on bone marrow cells from a patient with chronic lymphocytic leukemia (CLL) and secondary myelodysplasia. The G-banding analysis revealed the karyotype 46,XX,del(21)(q22)[9]/46,XX[2]...
2018: PloS One
https://www.readbyqxmd.com/read/29666622/chemotactic-cues-for-notch1-dependent-leukemia
#2
REVIEW
Erich Piovan, Valeria Tosello, Alberto Amadori, Paola Zanovello
The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29650518/secretory-igm-exacerbates-tumor-progression-by-inducing-accumulations-of-mdscs-in-mice
#3
Chih-Hang Anthony Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony R Mato, Juan R Del Valle, Dmitry Gabrilovich, Chih-Chi Andrew Hu
Chronic lymphocytic leukemia cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL...
April 12, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29569742/lenalidomide-as-immune-adjuvant-to-a-dendritic-cell-vaccine-in-chronic-lymphocytic-leukemia-patients
#4
Marzia Palma, Lotta Hansson, Tom A Mulder, Lars Adamson, Barbro Näsman-Glaser, Ingrid Eriksson, Kia Heimersson, Fariba Mozaffari, Ann Svensson, Giusy Gentilcore, Anders Österborg, Håkan Mellstedt
OBJECTIVES: We previously showed that immunization with ex-vivo generated autologous dendritic cells loaded with apoptotic tumor cells (Apo-DC) potentiated tumor-specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo-DC in combination with lenalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose cyclophosphamide (CTX). METHODS: Ten previously untreated patients with slowly progressing CLL received 5 Apo-DC vaccinations and lenalidomide orally for 24 weeks either alone (cohort I, n=5) or together with subcutaneous GM-CSF and intravenous CTX (cohort II, n=5)...
March 23, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29562857/obinutuzumab-induces-depletion-of-nk-cells-in-patients-with-chronic-lymphocytic-leukemia
#5
Ricardo García-Muñoz, Lorea Aguinaga, Jesus Feliu, Judit Anton-Remirez, Lorena Jorge-Del-Val, Andrea Casajús-Navasal, María José Nebot-Villacampa, Isabel Daroca-Fernandez, Elena Domínguez-Garrido, Pilar Rabasa, Carlos Panizo
AIM: Obinutuzumab induces NK cell antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: Investigate the effects on the human immune system after obinutuzumab monotherapy treatment in patients with chronic lymphocytic leukemia (CLL). METHOD: To evaluate these effects, we analyzed the distribution of CD4+ and CD8+ T cells, B cells and NK cells in the peripheral blood of eight CLL patients who were treated with obinutuzumab in monotherapy...
March 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29532605/hepatitis-b-virus-and-risk-of-non-hodgkin-lymphoma-an-updated-meta-analysis-of-58-studies
#6
Mengge Li, Yu Gan, Chunsun Fan, Hui Yuan, Xianjing Zhang, Yuling Shen, Qing Wang, Zihong Meng, Dengfei Xu, Hong Tu
Previous studies have focused on the relationship between hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). However, the results remain inconsistent and somehow conflicting in different sub-groups. The aim of this study was to combine the findings of independent studies to comprehensively assess the association between HBV and NHL using a meta-analysis. Relevant studies were identified through structured keyword searches in PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) database and 58 studies with a total of 53,714 NHL cases and 1,778,591 controls were finally included...
March 13, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29526569/elevated-levels-of-follicular-t-helper-cells-and-their-association-with-therapeutic-effects-in-patients-with-chronic-lymphocytic-leukaemia
#7
Liannv Qiu, Yonglie Zhou, Qinhua Yu, Sujie Zheng, Zhenni Wang, Qiang Huang
Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression...
March 8, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29504446/the-clinical-significance-of-b-cell-maturation-antigen-as-a-therapeutic-target-and-biomarker
#8
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
March 7, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29479062/distinct-roles-for-phosphoinositide-3-kinases-%C3%AE-and-%C3%AE-in-malignant-b-cell-migration
#9
Ahmed Y Ali, Xun Wu, Nour Eissa, Sen Hou, Jean-Eric Ghia, Thomas T Murooka, Versha Banerji, James B Johnston, Francis Lin, Spencer B Gibson, Aaron J Marshall
The PI 3-kinases (PI3K) are essential mediators of chemokine receptor signaling necessary for migration of chronic lymphocytic leukemia (CLL) cells and their interaction with tissue-resident stromal cells. While the PI3Kδ-specific inhibitor idelalisib shows efficacy in treatment of CLL and other B cell malignancies, the function of PI3Kγ has not been extensively studied in B cells. Here, we assess whether PI3Kγ has non-redundant functions in CLL migration and adhesion to stromal cells. We observed that pharmaceutical PI3Kγ inhibition with CZC24832 significantly impaired CLL cell migration, while dual PI3Kδ/γ inhibitor duvelisib had a greater impact than single isoform-selective inhibitors...
January 31, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29477371/venetoclax-a-new-wave-in-haemato-oncology
#10
REVIEW
Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek
Inhibitors of anti-apoptotic proteins of the BCL2 family can successfully restart the deregulated process of apoptosis in malignant cells. While non-selective agents have been limited by their affinity to different BCL2 members, and thus inducing excessive toxicity, the highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™), has an acceptable safety profile. To date, it has been approved in monotherapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) with 17p deletion...
February 22, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29476222/ibrutinib-brain-distribution-a-preclinical-study
#11
Lauriane Goldwirt, Kevin Beccaria, Alain Ple, Hélène Sauvageon, Samia Mourah
PURPOSE: Central nervous system (CNS) dissemination occurs in 4.1% of mantle cell lymphoma (MCL) patients and clinically significant CNS involvement in chronic lymphocytic leukemia (CLL) patients reaches 4%. Ibrutinib, an orally administered Bruton's tyrosine kinase (BTK) inhibitor, has shown substantial activity in CLL or MCL patients with CNS localization, and in primary central nervous system lymphoma (PCNSL). The drug efficacy to treat primary or secondary CNS impairments relies on its brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study the brain distribution of ibrutinib using an in vivo mice model...
February 23, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29467486/eric-recommendations-for-tp53-mutation-analysis-in-chronic-lymphocytic-leukemia-update-on-methodological-approaches-and-results-interpretation
#12
REVIEW
J Malcikova, E Tausch, D Rossi, L A Sutton, T Soussi, T Zenz, A P Kater, C U Niemann, D Gonzalez, F Davi, M Gonzalez Diaz, C Moreno, G Gaidano, K Stamatopoulos, R Rosenquist, S Stilgenbauer, P Ghia, S Pospisilova
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29450641/chronic-lymphocytic-leukemia-cells-acquire-regulatory-b-cell-properties-in-response-to-tlr9-and-cd40-activation
#13
Shimrit Ringelstein-Harlev, Irit Avivi, Mona Fanadka, Netanel A Horowitz, Tami Katz
Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia...
February 15, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29444977/microenvironmental-regulation-of-the-il-23r-il-23-axis-overrides-chronic-lymphocytic-leukemia-indolence
#14
Giovanna Cutrona, Claudio Tripodo, Serena Matis, Anna Grazia Recchia, Carlotta Massucco, Marina Fabbi, Monica Colombo, Laura Emionite, Sabina Sangaletti, Alessandro Gulino, Daniele Reverberi, Rosanna Massara, Simona Boccardo, Daniela de Totero, Sandra Salvi, Michele Cilli, Mariavaleria Pellicanò, Martina Manzoni, Sonia Fabris, Irma Airoldi, Francesca Valdora, Silvano Ferrini, Massimo Gentile, Ernesto Vigna, Sabrina Bossio, Laura De Stefano, Angela Palummo, Giovanni Iaquinta, Martina Cardillo, Simonetta Zupo, Giannamaria Cerruti, Adalberto Ibatici, Antonino Neri, Franco Fais, Manlio Ferrarini, Fortunato Morabito
Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rβ1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rβ1 chain when cocultured with activated T cells or CD40L+ cells...
February 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29434853/intracellular-il-4-and-ifn-%C3%AE-expression-in-inkt-cells-from-patients-with-chronic-lymphocytic-leukemia
#15
Agnieszka Bojarska-Junak, Małgorzata Waldowska, Justyna Woś, Sylwia Chocholska, Iwona Hus, Waldemar Tomczak, Michał Dzik, Marek Hus, Jacek Roliński
Malignant B cells in chronic lymphocytic leukemia serve an essential role in the whole immune response, so their interactions with other immune cells are more complex than observed in solid tumors. The latest study results indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) also affects a small population of invariant natural killer T cells (iNKT). Using peripheral blood iNKT cells obtained from patients with CLL, the objective of the present study was to assess the intracellular expression of typical cytokines involved in the Th1 (IFN-γ) and Th2 (IL-4) response pathways following stimulation with the iNKT-specific ligand α-galactosylceramide...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432497/autologous-t-cells-expressing-the-oncogenic-transcription-factor-klf6-sv1-prevent-apoptosis-of-chronic-lymphocytic-leukemia-cells
#16
Parviz Kokhaei, Mohammad Hojjat-Farsangi, Fariba Mozaffari, Ali Moshfegh, Fatemeh Pak, Ali Rashidy-Pour, Marzia Palma, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10)...
2018: PloS One
https://www.readbyqxmd.com/read/29428267/disseminated-cerebral-toxoplasmosis-in-a-patient-with-chronic-lymphocytic-leukemia
#17
Jordan Xu, Rod J Nault, Andres Maldonado-Naranjo, Leonardo A Frizon, Kuruvilla John, Katherine Holman, Sean J Nagel
Infections are one of the most common causes of mortality in immunocompromised patients. In patients diagnosed with hematologic malignancies, treatment with stem cell transplants (SCT) or T-cell suppressing chemotherapy increases the risk of central nervous system (CNS) infections, of which toxoplasmosis is the most common. We report the case of a 63 year-old woman with chronic lymphocytic leukemia (CLL) that presented with gait instability and visual changes. Intracranial lesions were noted on initial neuro-imaging...
February 7, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29415977/composite-lymphoma-as-co-occurrence-of-advanced-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-carrying-trisomy-12-and-t-14-18-and-peripheral-t-cell-lymphoma
#18
Yumi Aoyama, Taiichi Kodaka, Yuriko Zushi, Yuta Goto, Hiroko Tsunemine, Tomoo Itoh, Takayuki Takahashi
Composite lymphoma is defined as the co-occurrence of two types of lymphoma, comprising 1-4% of lymphomas, and the association of B-cell-type chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma and peripheral T-cell lymphoma (PTCL) is rare. Here, we report a case (77-year-old woman) of advanced B-CLL complicated by newly appearing PTCL. Two years after the onset of B-CLL, CLL cells acquired CD38 antigen expression and the disease entity became CLL/prolymphocytic leukemia. Trisomy 12 and t(14;18) karyotypes were observed...
February 8, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29390452/coexistence-of-t-2-14-11-p16-1-q32-q23-and-t-14-19-q32-q13-3-chromosome-translocations-in-a-patient-with-chronic-lymphocytic-leukemia-a-case-report
#19
Guangming Liu, Zhongmei Wen, Xianglan Lu, Young Mi Kim, Xianfu Wang, Rebecca M Crew, Mohamad A Cherry, Shibo Li, Yuanyuan Liu
RATIONALE: With combination of multiple techniques, we have successfully characterized unique, complex chromosomal changes in a patient with chronic lymphocytic leukemia (CLL), a lymphoproliferative disorder. DIAGNOSES: The diagnosis was based on white blood cell, flow cytometry, and immunophenotypes and confirmed by karyotype, fluorescence in situ hybridization, and array comparative genomic hybridization from the patient's blood culture. INTERVENTIONS: The patient was given fludarabine, cyclophosphamide and rituximab (FCR) for 6 cycles...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29371889/cytogenetic-mutation-profile-of-chronic-lymphocytic-leukemia-malignant-melanoma-collision-tumors-of-the-skin
#20
Roberta La Starza, Tiziana Pierini, Lorenza Pastorino, Elisa Albi, Caterina Matteucci, Barbara Crescenzi, Paolo Sportoletti, Piero Covarelli, Franca Falzetti, Giovanni Roti, Stefano Ascani, Cristina Mecucci
Background: Collision tumors are rare entities that consist of two histologically distinct tumor types arising in the same anatomic site. An association between chronic lymphocytic leukemia (CLL) and malignant melanoma (MM) has been already described. Up to now, they have been documented only at positive regional lymph nodes while we focused on collision tumor in a skin lesion. Case presentation: We characterized the genomic profile of a skin CLL/MM collision tumor in a patient with a 9-years story of CLL...
2018: Molecular Cytogenetics
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