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https://www.readbyqxmd.com/read/28203581/long-term-response-and-possible-cure-of-patients-with-b-cell-malignancies-with-dose-escalated-rituximab
#1
Lauren M Jacobs, Peter H Wiernik, Janice P Dutcher, Pablo Muxi
Rituximab (R), a chimeric monoclonal antibody targeting CD20 antigen on B-cells, has become a standard of care in the treatment of B-cell malignancies, most often in conjunction with cytotoxic chemotherapy. Activity has been demonstrated in many subtypes of B-cell lymphoma, including diffuse large cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), lymphocyte-predominant Hodgkin lymphoma, and Waldenström macroglobulinemia (WM). Additionally, dose escalation of R as a single agent has demonstrated improved activity in previously treated/poor prognosis CLL...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28197963/a-concise-review-of-autoimmune-cytopenias-in-chronic-lymphocytic-leukemia
#2
REVIEW
Mazie Tsang, Sameer A Parikh
Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia, and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and it involves antigen presentation by CLL cells to polyclonal B cells resulting in production of autoantibody, and alteration of the T cell milieu tilting the balance in favor of an autoimmune response...
February 14, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28191372/richter-transformation-of-chronic-lymphocytic-leukemia-a-review-of-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-and-molecular-diagnostics
#3
REVIEW
Faiq Shaikh, Amna Janjua, Frederick Van Gestel, Adeel Ahmad
Chronic lymphocytic leukemia (CLL) is a low-grade B-cell proliferative disease with a generally indolent course. In a few cases, it undergoes transformation and becomes a more aggressive malignancy, such as diffuse large B-cell lymphoma (DLBCL). This process, which is called Richter transformation (RT), is often detected too late and is associated with a poor prognosis. There are multiple molecular diagnostic approaches to detect RT in preexisting CLL. Metabolic imaging using 18-fluorine fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) can be a very useful tool for early detection of RT and which can hence allow for timely intervention, thereby improving the patient's chances of survival...
January 9, 2017: Curēus
https://www.readbyqxmd.com/read/28183684/prognosis-biomarkers-evaluation-in-chronic-lymphocytic-leukemia
#4
Lorena Caixeta Gomes, Fernanda Cristina Gontijo Evangelista, Lirlândia Pires de Sousa, Sergio Schusterschitz da Silva Araujo, Maria das Graças Carvalho, Adriano de Paula Sabino
OBJECTIVE/BACKGROUND: From clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28164634/cd38-expression-and-variation-as-a-prognostic-factor-chronic-lymphocytic-leukemia
#5
Mesude Falay, Funda Ceran, Ahmet K Gunes, Simten Dagdas, Meltem Ayli, Gulsum Ozet
BACKGROUND: In this study, we aimed to determine a cutoff level for CD38 that would aid us in identifying chronic lymphocytic leukemia patients in need of early therapy and predicting patients at sufficiently low risk who would likely exhibit a rapid improvement; we also aimed to find out if CD38 expression would show variability during disease course and determine the extent of CD38 expression. METHODS: 124 patients were diagnosed with CLL. CD38 and ZAP-70 expression levels were measured with four color flowcytometry...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28144729/development-of-acute-myeloid-leukemia-in-patients-with-untreated-chronic-lymphocytic-leukemia
#6
Shoko Ito, Shin-Ichiro Fujiwara, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4...
February 1, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28125682/the-number-of-overlapping-aid-hotspots-in-germline-ighv-genes-is-inversely-correlated-with-mutation-frequency-in-chronic-lymphocytic-leukemia
#7
Chaohui Yuan, Charles C Chu, Xiao-Jie Yan, Davide Bagnara, Nicholas Chiorazzi, Thomas MacCarthy
The targeting of mutations by Activation-Induced Deaminase (AID) is a key step in generating antibody diversity at the Immunoglobulin (Ig) loci but is also implicated in B-cell malignancies such as chronic lymphocytic leukemia (CLL). AID has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) hotspots. WGCW sites, which contain an overlapping WRC hotspot on both DNA strands, mutate at much higher frequency than single hotspots. Human Ig heavy chain (IGHV) genes differ in terms of WGCW numbers, ranging from 4 for IGHV3-48*03 to as many as 12 in IGHV1-69*01...
2017: PloS One
https://www.readbyqxmd.com/read/28112746/risk-factors-for-treatment-failure-after-allogeneic-transplantation-of-patients-with-cll-a-report-from-the-european-society-for-blood-and-marrow-transplantation
#8
J Schetelig, L C de Wreede, M van Gelder, N S Andersen, C Moreno, A Vitek, M Karas, M Michallet, M Machaczka, M Gramatzki, D Beelen, J Finke, J Delgado, L Volin, J Passweg, P Dreger, A Henseler, A van Biezen, M Bornhäuser, S O Schönland, N Kröger
For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%...
January 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28100842/prognostic-value-of-thymidine-kinase-activity-in-patients-with-chronic-lymphocytic-leukemia
#9
Piotr Stelmach, Jerzy Z Błoński
Thymidine kinase (TK) activity is a marker of biological activity that allows the indolent and aggressive forms of chronic lymphocytic leukemia (CLL) to be distinguished. The aims of the study were to determine the relationship between TK activity and clinical status and prognosis, as well as to compare its activity with that of other prognostic and predictive factors. TK activity was measured in patient sera at the time of diagnosis using the DiviTum method, with the mean value being 439 Du/L. A correlation was found between TK activity and risk of disease progression (p=0...
December 30, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28091403/chronic-lymphocytic-leukemia-prognostic-index-a-new-integrated-scoring-system-to-predict-the-time-to-first-treatment-in-chinese-patients-with-chronic-lymphocytic-leukemia
#10
Heng Li, Shu-Hua Yi, Wen-Jie Xiong, Hui-Min Liu, Rui Lyu, Ting-Yu Wang, Wei Liu, Shi-Zhen Zhong, Zhen Yu, De-Hui Zou, Yan Xu, Gang An, Zeng-Jun Li, Lu-Gui Qiu
BACKGROUND: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI)...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28075457/high-resolution-melting-analysis-for-rapid-and-sensitive-notch1-screening-in-chronic-lymphocytic-leukemia
#11
Jing-Jing Xu, Fei-Rong Yao, Min Jiang, You-Tao Zhang, Feng Guo
Chronic lymphocytic leukemia (CLL) is a biological and clinical heterogeneous disease. Activating mutations of NOTCH1 have been implicated to be associated with adverse prognosis in CLL. The objective of the present study was to develop an effective high-resolution melting (HRM) assay for detecting NOTCH1 mutations. Genomic DNA (gDNA) extracted from 133 CLL patients was screened by HRM assay, and the results were compared with the data obtained using direct sequencing. The relative sensitivity of the HRM assay and direct sequencing was evaluated using diluted gDNA with different NOTCH1 mutational frequencies...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28038857/similar-prognosis-of-transformed-and-de-novo-diffuse-large-b-cell-lymphomas-in-patients-treated-with-immunochemotherapy
#12
Marc Sorigue, Olga Garcia, Maria Joao Baptista, Juan-Manuel Sancho, Gustavo Tapia, José Luis Mate, Evarist Feliu, José-Tomás Navarro, Josep-Maria Ribera
BACKGROUND: The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. PATIENTS AND METHODS: We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. RESULTS: Patients with TL and de novo DLBCL had similar characteristics...
December 27, 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28038356/mrna-overexpression-of-the-hypoxia-inducible-factor-1-alpha-subunit-gene-hif1a-an-independent-predictor-of-poor-overall-survival-in-chronic-lymphocytic-leukemia
#13
Christos K Kontos, Sotirios G Papageorgiou, Marios A Diamantopoulos, Andreas Scorilas, Efthimia Bazani, Diamantina Vasilatou, Konstantinos Gkontopoulos, Eirini Glezou, Georgia Stavroulaki, George Dimitriadis, Vasiliki Pappa
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28017968/mutations-in-notch1-pest-domain-orchestrate-ccl19-driven-homing-of-chronic-lymphocytic-leukemia-cells-by-modulating-the-tumor-suppressor-gene-dusp22
#14
F Arruga, B Gizdic, C Bologna, S Cignetto, R Buonincontri, S Serra, T Vaisitti, K Gizzi, N Vitale, G Garaffo, E Mereu, F Diop, F Neri, D Incarnato, M Coscia, J Allan, R Piva, S Oliviero, R R Furman, D Rossi, G Gaidano, S Deaglio
Even if NOTCH1 is commonly mutated in Chronic Lymphocytic Leukemia (CLL), its functional impact in the disease remains unclear. Using CRISPR/Cas9-generated Mec-1 cell line models, we show that NOTCH1 regulates growth and homing of CLL cells by dictating expression levels of the tumor suppressor gene DUSP22. Specifically, NOTCH1 affects the methylation of DUSP22 promoter by modulating a nuclear complex, which tunes the activity of DNA methyltransferase 3A (DNMT3A). These effects are enhanced by PEST-domain mutations, which stabilize the molecule and prolong signaling...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28004597/functional-proteomic-insights-in-b-cell-chronic-lymphocytic-leukemia
#15
Paula Díez, Rafael Góngora, Alberto Orfao, Manuel Fuentes
B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease. Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described...
February 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/27959900/genomic-profile-of-chronic-lymphocytic-leukemia-in-korea-identified-by-targeted-sequencing
#16
Jung-Ah Kim, Byungjin Hwang, Si Nae Park, Sunghoon Huh, Kyongok Im, Sungbin Choi, Hye Yoon Chung, JooRyung Huh, Eul-Ju Seo, Je-Hwan Lee, Duhee Bang, Dong Soon Lee
Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications. We performed targeted sequencing for 87 gene panel using next-generation sequencing along with G-banding and fluorescent in situ hybridization (FISH) for chromosome 12, 13q14...
2016: PloS One
https://www.readbyqxmd.com/read/27928896/genomic-data-integration-in-chronic-lymphocytic-leukemia
#17
Juan Luis Fernández-Martínez, Enrique J deAndrés-Galiana, Stephen T Sonis
BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous disease and the most common adult leukemia in western countries. IgVH mutational status distinguishes two major types of CLL, each associated with a different prognosis and survival. Sequencing identified NOTCH1 and SF3B1 as the two main recurrent mutations. We described a novel method to clarify how these mutations affect gene expression by finding small-scale signatures that predict the IgVH, NOTCH1 and SF3B1 mutations...
January 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/27927769/integration-of-b-cell-receptor-induced-erk1-2-phosphorylation-and-mutations-of-sf3b1-gene-refines-prognosis-in-treatment-naive-chronic-lymphocytic-leukemia
#18
Chiara Cavallini, Carlo Visco, Santosh Putta, Davide Rossi, Elda Mimiola, Norman Purvis, Ornella Lovato, Omar Perbellini, Erika Falisi, Monica Facco, Livio Trentin, Maria G Romanelli, Gianpietro Semenzato, Achille Ambrosetti, Gianluca Gaidano, Giovanni Pizzolo, Alessandra Cesano, Maria T Scupoli
No abstract text is available yet for this article.
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27913474/prognostication-of-chronic-lymphocytic-leukemia-in-the-era-of-new-agents
#19
Barbara Eichhorst, Michael Hallek
The prognosis of chronic lymphocytic leukemia (CLL) is very heterogeneous. Therefore, a plethora of prognostic factors has been identified to allow a better prediction of the individual prognosis of a given patient. The clinical staging systems by Rai and Binet have been the backbone of clinical management for several decades. The advent of genetic and biochemical markers, as well as next-generation sequencing has provided several markers that can predict the prognosis of patients with CLL. Using this knowledge, several scores have been created to improve predicting overall survival and/or treatment-free survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27890934/egr2-mutations-define-a-new-clinically-aggressive-subgroup-of-chronic-lymphocytic-leukemia
#20
E Young, D Noerenberg, L Mansouri, V Ljungström, M Frick, L-A Sutton, S J Blakemore, J Galan-Sousa, K Plevova, P Baliakas, D Rossi, R Clifford, D Roos-Weil, V Navrkalova, B Dörken, C A Schmitt, K E Smedby, G Juliusson, B Giacopelli, J S Blachly, C Belessi, P Panagiotidis, N Chiorazzi, F Davi, A W Langerak, D Oscier, A Schuh, G Gaidano, P Ghia, W Xu, L Fan, O A Bernard, F Nguyen-Khac, L Rassenti, J Li, T J Kipps, K Stamatopoulos, S Pospisilova, T Zenz, C C Oakes, J C Strefford, R Rosenquist, F Damm
Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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