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Richter's transformation

Dagmara Jankowska, Tobias Heck, Mark Schubert, Alpaslan Yerlikaya, Christophe Weymuth, Daniel Rentsch, Irene Schober, Michael Richter
Lignin is the most abundant aromatic biopolymer functioning as an integral compound of woody materials. In its unmodified form it shows limited water solubility and is relatively unreactive. Thus, biotechnological lignin valorisation for high performance applications is highly underexploited. To expand its application, a new synthesis route towards novel concrete dispersing agents was developed. The route relies on a lignin functionalization by enzymatic transformation. Screening of lignin modifying systems resulted in functionalized lignin polymers with improved solubility in aqueous systems...
March 15, 2018: Chembiochem: a European Journal of Chemical Biology
Khadega A Abuelgasim, Hinna Rehan, Maha Alsubaie, Nasser Al Atwi, Mohammed Al Balwi, Saeed Alshieban, Areej Almughairi
BACKGROUND: Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases...
March 11, 2018: Journal of Medical Case Reports
Anja Müller, Bernd Gillissen, Antje Richter, Anja Richter, Cindrilla Chumduri, Peter T Daniel, Christian W Scholz
Constitutive signaling of PI3K/Akt/mTOR plays a prominent role in malignant transformation and progression of B-cell non-Hodgkin lymphomas (B-NHL) underscoring the need for PI3K targeted therapies. The pan-class I PI3-kinase inhibitor BKM120 has shown preclinical activity in distinct malignancies and is currently tested in clinical trials. Intratumor heterogeneity is an intrinsic property of cancers that contributes to drug resistance and tumor recurrence. Here, we demonstrate that inhibition of PI3-kinases by BKM120 attenuates growth and survival of B-NHL cell lines by inducing mitotic arrest with subsequent induction of intrinsic apoptosis...
March 7, 2018: Cell Death & Disease
Chieh-Lung Cheng, Yung-Cheng Su, Tsu-Yi Chao, Chung-Wu Lin, Sheng-Chieh Chou, Ming Yao, Sung-Hsin Kuo, Shan-Chi Yu
Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts...
March 2, 2018: American Journal of Surgical Pathology
Idanna Innocenti, Davide Rossi, Giulio Trapè, Francesco Autore, Luigi Maria Larocca, Vincenzo Gomes, Michaela Cerri, Paolo Falcucci, Simona Sica, Gianluca Gaidano, Luca Laurenti
Richter syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a diffuse large B-cell lymphoma, is a rare complication of patients treated with chemo-immunotherapy. Richter syndrome might be both clonally related or unrelated to the underlying CLL and often showed mutations of the TP53 and NOTCH1 genes. Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation. The clinical picture, pathology, and genetics of Richter transformation after IBR treatment are largely unknown...
February 27, 2018: Hematological Oncology
Maria J García-Barchino, Maria E Sarasquete, Carlos Panizo, Julie Morscio, Antonio Martinez, Miguel Alcoceba, Vicente Fresquet, Blanca Gonzalez-Farre, Bruno Paiva, Ken H Young, Eloy F Robles, Sergio Roa, Jon Celay, Marta Larrayoz, Davide Rossi, Gianluca Gaidano, Santiago Montes-Moreno, Miguel A Piris, Ana Balanzategui, Cristina Jimenez, Idoia Rodriguez, Maria J Calasanz, Maria J Larrayoz, Victor Segura, Ricardo Garcia-Muñoz, Maria P Rabasa, Shuhua Yi, Jianyong Li, Mingzhi Zhang, Zijun Y Xu-Monette, Noemi Puig-Moron, Alberto Orfao, Sebastian Böttcher, Jesus M Hernandez-Rivas, Jesus San Miguel, Felipe Prosper, Thomas Tousseyn, Xavier Sagaert, Marcos Gonzalez, Jose A Martinez-Climent
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine or other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In comparison to EBV-negative tumors, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL and exhibited CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal center DLBCL phenotype, EBV latency programs type II/III, and a very short survival...
February 21, 2018: Journal of Pathology
Stefan Fritz, Regina Küper-Steffen, Katharina Feilhauer, Christoph M Sommer, Götz M Richter, René Hennig, Jörg Köninger
RATIONALE: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are benign cystic tumors with a relevant risk of malignant transformation over time. Currently, follow-up after surgical resection of benign IPMNs remains controversial. PATIENT CONCERNS: This is a case report of a 68-year-old male who underwent pancreatic head resection for a multicystic side-branch IPMN with low-grade epithelial dysplasia in March 2009 at the Katharinenhospital Stuttgart, Germany...
February 2018: Medicine (Baltimore)
Maren Leifheit-Nestler, Felix Kirchhoff, Julia Nespor, Beatrice Richter, Birga Soetje, Michael Klintschar, Joerg Heineke, Dieter Haffner
Background: Fibroblast growth factor 23 (FGF23) is discussed as a new biomarker of cardiac hypertrophy and mortality in patients with and without chronic kidney disease (CKD). We previously demonstrated that FGF23 is expressed by cardiac myocytes, enhanced in CKD and induces cardiac hypertrophy via activation of FGF receptor 4 independent of its co-receptor klotho. The impact of FGF23 on cardiac fibrosis is largely unknown. Methods: By conducting a retrospective case-control study including myocardial autopsy samples from 24 patients with end-stage CKD and in vitro studies in cardiac fibroblasts and myocytes, we investigated the pro-fibrotic properties of FGF23...
February 7, 2018: Nephrology, Dialysis, Transplantation
Roma Srivastava, Doreen Griswold, Muhammad Omer Jamil
Herpes simplex virus (HSV) adenitis is a rare but important cause of morbidity in immunocompromised patients. Chronic lymphocytic leukaemia (CLL)/Small lymphocytic lymphoma (SLL) is an indolent disease which impairs the cellular and humoral immunity, predisposing patients to a myriad of infections. Clinically, herpetic adenitis can mimic large cell (Richter's) transformation in patients with CLL. To date, less than 30 cases of HSV adenitis have been reported in the literature. We report a case of a patient with CLL with no prior history of HSV infection, who presented with rapidly enlarging lymph nodes after initial response to idelalisib raising the suspicion of Richter's transformation...
February 2, 2018: BMJ Case Reports
Bartlomiej M Getta, Sean Devlin, Jae H Park, Martin S Tallman, Ellin Berman
Outcomes in very young CLL patients (age ≤40) are not well characterized. We compared 71 consecutive patients aged ≤40 with 142 "older" matched patients >40 from our institution and used SEER database as an independent comparison group. Patients in the two age groups were diagnosed at similar Rai stage. At diagnosis, very young patients had a similar rate of adverse cytogenetics, IGHV mutation and ZAP70 expression and had lower beta-2-microglobulin and a lower incidence of second malignancies...
February 2018: Leukemia Research
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
Sabah Kadri, Jimmy Lee, Carrie Fitzpatrick, Natalie Galanina, Madina Sukhanova, Girish Venkataraman, Shruti Sharma, Brad Long, Kristin Petras, Megan Theissen, Mei Ming, Yuri Kobzev, Wenjun Kang, Ailin Guo, Weige Wang, Nifang Niu, Howard Weiner, Michael Thirman, Wendy Stock, Sonali M Smith, Chadi Nabhan, Jeremy P Segal, Pin Lu, Y Lynn Wang
Ibrutinib has generated remarkable responses in patients with chronic lymphocytic leukemia (CLL), including those with an unfavorable cytogenetic profile. However, patients develop resistance, with poor outcomes and no established treatment options. Mutations in BTK and PLCG2 have emerged as main mechanisms of drug resistance, but not all patients carry these mutations. Further understanding of mechanisms of resistance is urgently needed and will support rational development of new therapeutic strategies. To that end, we characterized the genomic profiles of serial samples from 9 patients with ibrutinib-relapsed disease, including 6 who had Richter transformation...
May 9, 2017: Blood Advances
Jeffrey A Jones, Anthony R Mato, William G Wierda, Matthew S Davids, Michael Choi, Bruce D Cheson, Richard R Furman, Nicole Lamanna, Paul M Barr, Lang Zhou, Brenda Chyla, Ahmed Hamed Salem, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, Steven Coutre, Jennifer Woyach, John C Byrd
BACKGROUND: Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy...
December 12, 2017: Lancet Oncology
L Richter, M-L Samuels
BACKGROUND: South Africa is the first sub-Saharan African country to legislate, fund and implement free preschool education. Human rights and restitution were at the forefront of the political struggle for democracy in South Africa. Levelling the playing fields by improving the school readiness of children disadvantaged by the racist policies of Apartheid is essential to the transformation of South African society. METHODS: A review of published and unpublished documents on Grade R was undertaken, and access and enrolment data come from the National Department of Basic Education's Education Management Information System (EMIS)...
January 2018: Child: Care, Health and Development
Pei-Pei Kung, Patrick Bingham, Alexei Brooun, Michael Collins, Ya-Li Deng, Dac Dinh, Connie Fan, Ketan S Gajiwala, Rita Grantner, Hovhannes J Gukasyan, Wenyue Hu, Buwen Huang, Robert Kania, Susan E Kephart, Cody Krivacic, Robert A Kumpf, Penney Khamphavong, Manfred Kraus, Wei Liu, Karen A Maegley, Lisa Nguyen, Shijian Ren, Dan Richter, Robert A Rollins, Neal Sach, Shikhar Sharma, John Sherrill, Jillian Spangler, Albert E Stewart, Scott Sutton, Sean Uryu, Dominique Verhelle, Hui Wang, Shuiwang Wang, Martin Wythes, Shuibo Xin, Shinji Yamazaki, Huichun Zhu, JinJiang Zhu, Luke Zehnder, Martin Edwards
A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp3 hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group. This transformation enabled optimization of the physicochemical properties and potency compared to compound 1...
February 8, 2018: Journal of Medicinal Chemistry
Norbert Pfeiffer, Bogomil Voykov, Giulia Renieri, Katharina Bell, Paul Richter, Melanie Weigel, Hagen Thieme, Barbara Wilhelm, Katrin Lorenz, Martin Feindor, Katja Wosikowski, Michel Janicot, Daniela Päckert, Regina Römmich, Carola Mala, Petra Fettes, Eugen Leo
PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6...
2017: PloS One
Adalgisa Condoluci, Davide Rossi
Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50-60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a18 FDG PET/CT and a biopsy are recommended to confirm RS...
November 21, 2017: Current Treatment Options in Oncology
Dariusz Szczepanek, Ewa Wąsik-Szczepanek, Agnieszka Szymczyk, Małgorzata Wach, Maria Cioch, Monika Podhorecka, Ewelina Grywalska, Marek Hus
Inclusion of the central nervous system (CNS) in the course of chronic lymphocytic leukaemia (CLL) is rare. At the moment no risk factors or proven treatment methods are known. The disease is described both in its early phase and during its acceleration period, thus it has been suggested that there might be independent mechanisms influencing the development of this condition. As there are no unified diagnostic procedure algorithms each patient needs to be assessed individually. CLL can manifest mostly in elderly people, for whom a possibility of development of neurological disorders with their aetiology different from leukaemia, should also be taken into consideration...
November 1, 2017: Neurologia i Neurochirurgia Polska
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials...
January 4, 2018: Blood
Maliha Khan, Rabbia Siddiqi, Philip A Thompson
Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2-10% of CLL patients develop aggressive histological transformation, most commonly to diffuse large B cell lymphoma (DLBCL), historically called Richter transformation (RT). Clinical features suggestive of RT include elevated LDH and non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18-fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake value max most commonly ≥ 10). PET/CT study can identify optimal site for excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in disease staging and prognostication...
January 2018: Annals of Hematology
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