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https://www.readbyqxmd.com/read/29905151/chronic-lymphocytic-leukemia-with-t-14-18-and-trisomy-12-a-case-report
#1
Maïlys Le Guyader, Marie Coude, Kamel Laribi, Anne Besançon, Habib Ghnaya, Nathalie Denizon, Sabine Defasque, Fabienne Pineau-Vincent, Mohamed Kaabar, Pierre Lemaire
Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm defined by the presence of at least 5×109 G/L monoclonal B lymphocytes in the peripheral blood. It is the most common type of leukemia in adult patients from Western countries. CLL is characterized by a gradual accumulation of small, longliving, immunologically dysfunctional, morphologically mature-appearing B-lymphocytes in blood, bone marrow and lymphoid tissues. It has also been reported that CLL cells have a proliferation rate higher than previously recognized, particularly in the lymphoid tissues...
June 15, 2018: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29899864/potent-anti-leukemic-activity-of-a-specific-cyclin-dependent-kinase-9-inhibitor-in-mouse-models-of-chronic-lymphocytic-leukemia
#2
Joachim R Göthert, Roze Imsak, Michael Möllmann, Stefanie Kesper, Maria Göbel, Ulrich Dührsen, Arne Scholz, Ulrich Lücking, Matthias Baumann, Anke Unger, Carsten Schultz-Fademrecht, Bert Klebl, Jan Eickhoff, Axel Choidas, Jan Dürig
Onset of progression even during therapy with novel drugs remains an issue in chronic lymphocytic leukemia (CLL). Thus, there is ongoing demand for novel agents. Approaches targeting cyclin-dependent kinases (CDK) have reached the clinical trial stage. CDK9 mediating RNA transcriptional elongation is the evolving pivotal CLL CDK inhibitor target. However, more CDK9 selective compounds are desirable. Here, we describe the CDK9 inhibitor LDC526 displaying a low nanomolar biochemical activity against CDK9 and an at least 50-fold selectivity against other CDKs...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899828/efficient-lysis-of-b-chronic-lymphocytic-leukemia-cells-by-the-plant-derived-sesquiterpene-alcohol-%C3%AE-bisabolol-a-dual-proapoptotic-and-antiautophagic-agent
#3
Antonella Rigo, Isacco Ferrarini, Angela Bonalumi, Cristina Tecchio, Alessio Montresor, Carlo Laudanna, Fabrizio Vinante
The sesquiterpene α-bisabolol (α-BSB) is a cytotoxic agent against acute leukemia and chronic myeloid leukemia cells. Here the profile of α-BSB citotoxicity was evaluated ex vivo in primary mononuclear blood cells isolated from 45 untreated B-chronic lymphocytic leukemia (B-CLL) patients. We studied the effects of α-BSB by flow cytometric and western blotting techniques with the following findings: (1) α-BSB was an effective proapoptotic agent against B-CLL cells (IC50 42 ± 15 μM). It was also active, but to a lesser extent, on normal residual B cells and monocytes (IC50 68 ± 34 and 74 ± 28 μM, respectively; p < 0...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29897892/a-t-18-22-q21-q11-involving-igl-bcl2-a-rare-event-in-chronic-lymphocytic-leukemia
#4
A Dowiak, Carlos A Tirado
We report a 63-year-old male whose bone marrow morphology and flow cytometry showed evidence of B-Chronic Lymphocytic Leukemia (B-CLL). Chromosome analysis of the bone marrow showed an abnormal karyotype, described as 46,XY,t(18;22)(q21;q11.2)[19]/46,XY[1]. FISH analysis on interphase nuclei revealed an abnormal clone with loss of D13S319 (13q14.3) in 68.0% of the cells examined. Deletion of chromosome 13 is the most common cytogenetic abnormality identified in CLL (approximately 50% of CLL). Recent studies suggest that deletion of chromosome 13q14 in 65% or more nuclei by FISH is associated with an intermediate to unfavorable prognosis in CLL...
2018: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/29893517/relationship-between-the-expression-of-cd25-and-cd69-on-the-surface-of-lymphocytes-t-and-b-from-peripheral-blood-and-bone-marrow-of-patients-with-chronic-lymphocytic-leukemia-and-established-prognostic-factors-of-this-disease
#5
Ewelina Grywalska, Małgorzata Bartkowiak-Emeryk, Marcin Pasiarski, Karolina Olszewska-Bożek, Michał Mielnik, Martyna Podgajna, Monika Pieczykolan, Anna Hymos, Elżbieta Fitas, Agata Surdacka, Stanisław Góźdź, Jacek Roliński
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a condition characterized by the accumulation of morphologically mature monoclonal lymphocytes B with the CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The clinical course of patients with CLL is heterogeneous, ranging from indolent to aggressive. The role of lymphocyte activation in the natural history of CLL is still a matter of discussion. OBJECTIVES: The aim of this study was to determine the percentages and absolute numbers of lymphocytes B and T in peripheral blood and bone marrow of CLL patients...
June 12, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29884725/-tet2-disruption-enhances-the-efficacy-of-cd19-car-t-cell-therapy
#6
(no author information available yet)
Expansion of a single CAR T-cell clone triggers a complete remission in a patient with CLL.
June 8, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29880613/real-world-outcomes-and-management-strategies-for-venetoclax-treated-chronic-lymphocytic-leukemia-patients-in-the-united-states
#7
Anthony R Mato, Meghan Thompson, John N Allan, Danielle M Brander, John M Pagel, Chaitra S Ujjani, Brian T Hill, Nicole Lamanna, Frederick Lansigan, Ryan Jacobs, Mazyar Shadman, Alan P Skarbnik, Jeffrey J Pu, Paul M Barr, Alison R Sehgal, Bruce D Cheson, Clive S Zent, Hande H Tuncer, Stephen J Schuster, Peter V Pickens, Nirav N Shah, Andre Goy, Allison M Winter, Christine Garcia, Kaitlin Kennard, Krista Isaac, Colleen Dorsey, Lisa M Gashonia, Arun K Singavi, Lindsey E Roeker, Andrew Zelenetz, Annalynn Williams, Christina Howlett, Hanna Weissbrot, Naveed Ali, Sirin Khajavian, Andrea Sitlinger, Eve Tranchito, Joanna Rhodes, Joshua Felsenfeld, Neil Bailey, Bhavisha Patel, Timothy F Burns, Melissa Yacur, Mansi Malhotra, Jakub Svoboda, Richard R Furman, Chadi Nabhan
Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26...
June 7, 2018: Haematologica
https://www.readbyqxmd.com/read/29872586/gastric-carcinoma-in-a-patient-with-chronic-lymphocytic-leukemia-coincidence-or-consequence
#8
Mayank Mangal, Sundaramurthi Sudharsanan, T P Elamurugan, Sadasivan Jagdish
Chronic lymphocytic leukemia (CLL) is a neoplasm of mature B-cells of unknown etiology. There is a site-specific increased incidence of second malignancy in patients with CLL. Leukemia and cancer can thus occur in the same patient either simultaneously or sequentially. We present a case of gastric adenocarcinoma in a patient with chronic lymphocytic leukemia. A 47-year old female presented with a history of abdominal pain for one year, along with nausea and vomiting for two months. On examination, she was pale and had generalized lymphadenopathy...
April 2, 2018: Curēus
https://www.readbyqxmd.com/read/29872562/restricted-t-cell-receptor-repertoire-in-cll-like-monoclonal-b-cell-lymphocytosis-and-early-stage-cll
#9
Gonzalo Blanco, Anna Vardi, Anna Puiggros, Andrea Gómez-Llonín, Manuel Muro, María Rodríguez-Rivera, Evangelia Stalika, Eugenia Abella, Eva Gimeno, Manuela López-Sánchez, Alicia Senín, Xavier Calvo, Pau Abrisqueta, Francesc Bosch, Ana Ferrer, Kostas Stamatopoulos, Blanca Espinet
Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4+ and CD8+ T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4+ T cell clonal expansions whose frequency followed the numerical increase of clonal B cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29862437/fludarabine-and-rituximab-with-escalating-doses-of-lenalidomide-followed-by-lenalidomide-rituximab-maintenance-in-previously-untreated-chronic-lymphocytic-leukaemia-cll-the-revlirit-cll-5-agmt-phase-i-ii-study
#10
Alexander Egle, Michael Steurer, Thomas Melchardt, Lukas Weiss, Franz Josef Gassner, Nadja Zaborsky, Roland Geisberger, Kemal Catakovic, Tanja Nicole Hartman, Lisa Pleyer, Daniela Voskova, Josef Thaler, Alois Lang, Michael Girschikofsky, Andreas Petzer, Richard Greil
Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found...
June 4, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29850623/analysis-of-ror1-protein-expression-in-mice-with-reconstituted-human-immune-system-components
#11
Carol S Leung
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen expressed on multiple tumors and has no significant expression on normal human tissues. ROR1 is highly upregulated in chronic lymphocytic leukemia (CLL) B cells. NOD-scid IL2rg-/- (NSG) mice engrafted with human CD34+ hematopoietic progenitor cells (huNSG) achieved multilineage human immune cell reconstitution including B cells, T cells, NK cells, and DCs. Like the CLL patients, huNSG mice have abnormally high percentage of CD5-expressing B cells in the periphery...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29806244/cd200-is-a-useful-diagnostic-marker-for-identifying-atypical-chronic-lymphocytic-leukemia-by-flow-cytometry
#12
Y S Ting, S A B C Smith, D A Brown, A J Dodds, K C Fay, D D F Ma, S Milliken, J J Moore, W A Sewell
INTRODUCTION: Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. METHODS: CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers...
May 27, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29796007/b-chronic-lymphocytic-leukemia-showed-triple-transformation-to-diffuse-large-b-cell-cd20-negative-and-t-cell-neoplasm-during-ofatumumab-treatment-a-case-report
#13
Osamu Imataki, Makiko Uemura
Background: Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter's syndrome. Case presentation: We treated a 69-year-old Japanese male who was histologically diagnosed with Richter's syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/μL and a disease status of Rai classification stage I and Binet classification B...
2018: BMC Clinical Pathology
https://www.readbyqxmd.com/read/29783667/bone-marrow-defects-and-platelet-function-a-focus-on-mds-and-cll
#14
REVIEW
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#15
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#16
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29764250/immunological-changes-with-kinase-inhibitor-therapy-for-chronic-lymphocytic-leukemia
#17
Christopher Pleyer, Adrian Wiestner, Clare Sun
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib...
May 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29756258/a-prospective-analysis-of-circulating-saturated-and-monounsaturated-fatty-acids-and-risk-of-non-hodgkin-lymphoma
#18
Yu-Han Chiu, Kimberly A Bertrand, Shumin Zhang, Francine Laden, Mara M Epstein, Bernard A Rosner, Stephanie Chiuve, Hannia Campos, Edward L Giovannucci, Jorge E Chavarro, Brenda M Birmann
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29743179/a-cd19-cd3-bispecific-antibody-for-effective-immunotherapy-of-chronic-lymphocytic-leukemia-in-the-ibrutinib-era
#19
Hannah R Robinson, Junpeng Qi, Erika M Cook, Cydney Nichols, Eman L Dadashian, Chingiz Underbayev, Sarah E M Herman, Nakhle S Saba, Keyvan Keyvanfar, Clare Sun, Inhye E Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29735552/hla-class-i-and-ii-diversity-contributes-to-the-etiologic-heterogeneity-of-non-hodgkin-lymphoma-subtypes
#20
Sophia S Wang, Mary Carrington, Sonja I Berndt, Susan L Slager, Paige M Bracci, Jenna Voutsinas, James R Cerhan, Karin Ekström Smedby, Henrik Hjalgrim, Joseph Vijai, Lindsay M Morton, Roel Vermeulen, Ora Paltiel, Claire M Vajdic, Martha S Linet, Alexandra Nieters, Silvia de Sanjosé, Wendy Cozen, Elizabeth E Brown, Jennifer Turner, John J Spinelli, Tongzhang Zheng, Brenda M Birmann, Christopher R Flowers, Nikolaus Becker, Elizabeth A Holly, Eleanor Kane, Dennis Weisenburger, Marc Maynadie, Pierluigi Cocco, Demetrius Albanes, Stephanie J Weinstein, Lauren R Teras, W Ryan Diver, Stephanie J Lax, Ruth C Travis, Rudolf Kaaks, Elio Riboli, Yolanda Benavente, Paul Brennan, James D McKay, Marie Helene Delfau-Larue, Brian K Link, Corrado Magnani, Maria G Ennas, Giancarlo Latte, Andrew L Feldman, Nicole Wong Doo, Graham G Giles, Melissa C Southey, Roger L Milne, Kenneth Offit, Jacob Muskinsky, Alan A Arslan, Mark P Purdue, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Lucia Conde, Nicola J Camp, Martha Glenn, Karen Curtin, Jacqueline Clavel, Alain Monnereau, David G Cox, Hervé Ghesquières, Gilles Salles, Paolo Boffetta, Lenka Foretova, Anthony Staines, Scott Davis, Richard K Severson, Qing Lan, Angela Brooks-Wilson, Martyn T Smith, Eve Roman, Anne Kricker, Yawei Zhang, Peter Kraft, Stephen J Chanock, Nathaniel Rothman, Patricia Hartge, Christine F Skibola
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent...
May 7, 2018: Cancer Research
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