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https://www.readbyqxmd.com/read/29352719/prognostic-testing-patterns-and-outcomes-of-chronic-lymphocytic-leukemia-patients-stratified-by-fluorescence-in-situ-hybridization-cytogenetics-a-real-world-clinical-experience-in-the-connect-cll-registry
#1
Anthony Mato, Chadi Nabhan, Neil E Kay, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Christopher R Flowers, Charles M Farber, Matthew S Davids, Pavel Kiselev, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. PATIENTS AND METHODS: In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed...
December 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#2
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29349871/dsp30-and-interleukin-2-as-a-mitotic-stimulant-in-b-cell-disorders-including-those-with-a-low-disease-burden
#3
Karen A Dun, Louise A Riley, Giuseppe Diano, Leanne B Adams, Eleanor Chiu, Archna Sharma
Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, predominantly in chronic lymphocytic leukaemia (CLL) but also a range of other B-cell malignancies...
January 19, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29349770/retrospective-audit-of-patients-referred-for-further-treatment-following-mohs-surgery-for-non-melanoma-skin-cancer
#4
Edmund Wee, Michelle S Goh, Vanessa Estall, Albert Tiong, Angela Webb, Catherine Mitchell, William Murray, Phillip Tran, Christopher J McCormack, Michael Henderson, Emma L Hiscutt
BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck...
January 18, 2018: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/29346066/expression-of-autophagy-related-genes-in-chronic-lymphocytic-leukemia-is-associated-with-disease-course
#5
Yi-Lin Kong, Ying Huang, Jia-Zhu Wu, Xin Cao, Jin-Hua Liang, Yi Xia, Wei Wu, Lei Cao, Hua-Yuan Zhu, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu
Autophagy leads cells to different fates in various cell types and under diverse contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm, has highly variable course and its heterogeneity prompts interest in exploring autophagic trajectories in CLL. We detected the mRNA levels of two autophagy-related genes, BECN1 and ATG5, assessed the association between expression levels and clinical characteristics, and did survival analysis. One hundred and six patients with CLL and fifty healthy controls were enrolled in the present study...
January 3, 2018: Leukemia Research
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
#6
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/29341235/concomitant-cutaneous-squamous-cell-carcinoma-and-cll-in-a-patient-the-utility-of-18-f-fdg-pet-ct-in-differentiation-of-nodal-metastasis
#7
Kerem Ozturk, Celalettin Ustun, Sobia Khaja, Faqian Li, Matthew Rischall, Zuzan Cayci
INTRODUCTION: Head and neck cutaneous squamous cell carcinoma (cSCC) often presents with cervical lymph node metastases. Lymphoma is the second most common malignancy in the cervical region, however, it is rarely synchronous with head and neck cSCC. METHODS: We describe the unusual presentation of a patient with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and metastatic head and neck cSCC on 18-fluorodeoxyglucose positron emission tomography (18 F-FDG PET/CT)...
January 17, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29338825/efficacy-of-rituximab-for-patients-with-chronic-lymphocytic-leukemia
#8
Heng Li, Wen Jie Xiong, Hui Min Liu, Shu Hua Yi, Rui Lü, Ting Yu Wang, Zhen Yu, Lu Gui Qiu, Zeng Jun Li
Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43...
December 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29333021/efficacy-and-safety-of-ibrutinib-in-indian-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia-and-mantle-cell-lymphoma-cases-from-a-named-patient-program
#9
Mohan B Agarwal, Dinesh Bhurani, Chirag Shah, Nitin Sood, Manish Singhal, Anil Kamat, Subash Chezhian, Suryaprakash Mishra, Dinesh Nagrale
Context: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29328450/mybl2-protects-against-h9c2-injury-induced-by-hypoxia-via-akt-and-nf%C3%A2-%C3%AE%C2%BAb-pathways
#10
Mingfeng Shao, Zexiang Ren, Rongjun Zhang
Cardiovascular diseases have become one of the major public health problems in many countries. The downregulation of MYBL2 was found in H9c2 and native cardiomyocytes cells after hypoxia treatment. The present study aimed to investigate the effects of MYB proto‑oncogene like 2 (MYBL2) on H9c2 injury induced by hypoxia. Reverse transcription‑quantitative polymerase chain reaction and western blot were performed on H9c2 cells to determine the mRNA and protein levels of MYBL2, respectively. Small interfering RNA (siRNA) was employed to downregulate MYBL2 expression in H9c2 cells to investigate changes in cell proliferation and apoptosis...
January 8, 2018: Molecular Medicine Reports
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
#11
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/29326230/base-resolution-analysis-of-dna-methylation-patterns-downstream-of-dnmt3a-in-mouse-na%C3%A3-ve-b-cells
#12
Christopher G Duncan, Hrisavgi D Kondilis-Mangum, Sara A Grimm, Pierre R Bushel, Kaliopi Chrysovergis, John D Roberts, Frederick L Tyson, B Alex Merrick, Paul A Wade
The DNA methyltransferase, Dnmt3a, is dynamically regulated throughout mammalian B cell development and upon activation by antigenic stimulation. Dnmt3a inactivation in hematopoietic stem cells has been shown to drive B cell-related malignancies, including chronic lymphocytic leukemia (CLL), and associates with specific DNA methylation patterns in transformed cells. However, while it is clear that inactivation of Dnmt3a in hematopoietic stem cells has profound functional impacts, the consequences of Dnmt3a inactivation in cells of the B lineage are unclear...
January 11, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29323237/racial-differences-in-four-leukemia-subtypes-comprehensive-descriptive-epidemiology
#13
Yinjun Zhao, Yu Wang, Shuangge Ma
Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320898/did-i-miss-it-discovering-hidden-coexisting-hematological-neoplasms-a-single-institutional-review-of-100-collision-tumors
#14
Evan Himchak, Etan Marks, Yang Shi, Yanhua Wang
A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29318593/optimising-outcomes-for-patients-with-chronic-lymphocytic-leukaemia-on-ibrutinib-therapy-european-recommendations-for-clinical-practice
#15
John G Gribben, Francesc Bosch, Florence Cymbalista, Christian H Geisler, Paolo Ghia, Peter Hillmen, Carol Moreno, Stephan Stilgenbauer
Ibrutinib is indicated in Europe for the treatment of several B-cell malignancies, including chronic lymphocytic leukaemia (CLL). However, despite the high efficacy and favourable toxicity profile of ibrutinib, recent data suggest that it is not always administered optimally in clinical practice, with an increased tendency for dose reduction and a higher frequency of discontinuation. An expert panel of European haematologists was convened to identify practical issues pertinent to physicians involved in the therapeutic management of ibrutinib-treated CLL patients and here we outline the findings...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29317997/experience-with-ibrutinib-for-first-line-use-in-patients-with-chronic-lymphocytic-leukemia
#16
REVIEW
Gilad Itchaki, Jennifer R Brown
Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29317636/the-expression-of-inhibitor-of-bruton-s-tyrosine-kinase-gene-is-progressively-up-regulated-in-the-clinical-course-of-chronic-lymphocytic-leukaemia-conferring-resistance-to-apoptosis
#17
Francesco Albano, Federico Chiurazzi, Selena Mimmi, Eleonora Vecchio, Arianna Pastore, Clementina Cimmino, Camilla Frieri, Enrico Iaccino, Antonio Pisano, Gaetanina Golino, Giuseppe Fiume, Massimo Mallardo, Giuseppe Scala, Ileana Quinto
Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton's tyrosine kinase-isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression of IBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission...
January 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29317454/casein-kinase-1-is-a-therapeutic-target-in-chronic-lymphocytic-leukemia
#18
Pavlina Janovska, Jan Verner, Jiri Kohoutek, Lenka Bryjova, Michaela Gregorova, Marta Dzimkova, Hana Skabrahova, Tomasz Radaszkiewicz, Petra Ovesna, Olga Vondalova Blanarova, Tereza Nemcova, Zuzana Hoferova, Katerina Vasickova, Lucie Smyckova, Alexander Egle, Sarka Pavlova, Lucie Poppova, Karla Plevova, Sarka Pospisilova, Vitezslav Bryja
Casein kinase (CK) 1δ/ε is a key component of non-canonical Wnt signaling pathways, which were shown previously to drive pathogenesis of chronic lymphocytic leukemia (CLL). In this study we investigated thoroughly the effects of CK1δ/ε inhibition on the primary CLL cells and analyzed the therapeutic potential in vivo using two murine model systems based on the Eµ-TCL1-induced leukemia (syngeneic adoptive transfer model and spontaneous disease development), which resemble closely the human CLL. We can demonstrate that CK1δ/ε inhibitor PF-670462 significantly blocks microenvironmental interactions - chemotaxis, invasion and communication with stromal cells in primary CLL cells in all major subtypes of CLL...
January 9, 2018: Blood
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#19
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/29316610/development-of-a-deimmunized-bispecific-immunotoxin-ddt2219-against-b-cell-malignancies
#20
Joerg U Schmohl, Deborah Todhunter, Elizabeth Taras, Veronika Bachanova, Daniel A Vallera
Diphtheria toxin (DT) related targeted toxins are effective in cancer treatment, but efficacy diminishes in time because of their immunogenic potential and/or former vaccinations. In order to overcome this limitation for DT2219, a promising bispecific targeted toxin which targets CD19 and CD22, we deimmunized the DT moiety, and thereby developed an exciting improved drug (dDT2219) which still has the potential to sufficiently target B-cell malignancies but also limits clearance because of its reduced immunogenicity...
January 6, 2018: Toxins
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