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Richter's transformation

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https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#1
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29745101/simulations-of-centriole-of-polarized-centrosome-as-a-monopole-antenna-in-immune-and-viral-synapses
#2
Josef Dvorak, Bohuslav Melichar, Alzbeta Filipova, Jana Grimova, Nela Grimova, Aneta Rozsypalova, David Buka, Rene Voboril, Radek Zapletal, Tomas Buchler, Igor Richter, David Buka
The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29740608/time-resolved-structural-evolution-during-the-collapse-of-responsive-hydrogels-the-microgel-to-particle-transition
#3
Rico Keidel, Ali Ghavami, Dersy M Lugo, Gudrun Lotze, Otto Virtanen, Peter Beumers, Jan Skov Pedersen, Andre Bardow, Roland G Winkler, Walter Richtering
Adaptive hydrogels, often termed smart materials, are macromolecules whose structure adjusts to external stimuli. Responsive micro- and nanogels are particularly interesting because the small length scale enables very fast response times. Chemical cross-links provide topological constraints and define the three-dimensional structure of the microgels, whereas their porous structure permits fast mass transfer, enabling very rapid structural adaption of the microgel to the environment. The change of microgel structure involves a unique transition from a flexible, swollen finite-size macromolecular network, characterized by a fuzzy surface, to a colloidal particle with homogeneous density and a sharp surface...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29728606/structure-and-mechanism-of-the-two-component-%C3%AE-helical-pore-forming-toxin-yaxab
#4
Bastian Bräuning, Eva Bertosin, Florian Praetorius, Christian Ihling, Alexandra Schatt, Agnes Adler, Klaus Richter, Andrea Sinz, Hendrik Dietz, Michael Groll
Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex...
May 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29653431/inhibition-of-nampt-sensitizes-molt4-leukemia-cells-for-etoposide-treatment-through-the-sirt2-p53-pathway
#5
Theresa Grohmann, Melanie Penke, Stefanie Petzold-Quinque, Susanne Schuster, Sandy Richter, Wieland Kiess, Antje Garten
NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in the NAD biosynthesis from nicotinamide and thereby regulates the activity of NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and DNA repair processes and are assumed to be more susceptible to an inhibition of NAD synthesis than non-transformed cells. We aimed to investigate whether or not inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia cell lines compared to normal peripheral blood mononuclear cells...
April 5, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29568782/proteinuria-hypoalbuminemia-and-chronic-lymphocytic-leukemia-an-unusual-trio
#6
William Wung, Shubha Ananthakrishnan, Brian A Jonas
Chronic lymphocytic leukemia (CLL) is a chronic, progressive lymphoproliferative disorder characterized by a monoclonal population of functionally incompetent lymphocytes. Renal involvement is rare and poorly described. A 57-year-old male with no prior medical history was diagnosed with CLL and followed with a watch and wait approach. He was referred to our institution several months later due to concern for Richter's transformation to diffuse large B-cell lymphoma. A positron emission tomography/computed tomography scan showed no evidence of diffuse large B-cell lymphoma; however, the patient was noted to have hypoalbuminemia, nephrotic range proteinuria, an acute left renal vein thrombus, and a right pulmonary embolus...
January 2018: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29543396/enzymatic-synthesis-of-lignin-based-concrete-dispersing-agents
#7
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
https://www.readbyqxmd.com/read/29524963/coexistence-of-chronic-myeloid-leukemia-and-diffuse-large-b-cell-lymphoma-with-antecedent-chronic-lymphocytic-leukemia-a-case-report-and-review-of-the-literature
#8
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
https://www.readbyqxmd.com/read/29515122/pan-class-i-pi3-kinase-inhibitor-bkm120-induces-mek1-2-dependent-mitotic-catastrophe-in-non-hodgkin-lymphoma-leading-to-apoptosis-or-polyploidy-determined-by-bax-bak-and-p53
#9
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
https://www.readbyqxmd.com/read/29505426/intralymphatic-spread-is-a-rare-finding-associated-with-poor-prognosis-in-diffuse-large-b-cell-lymphoma-with-extranodal-involvements
#10
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...
May 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29484684/clinical-pathological-and-biological-characterization-of-richter-syndrome-developing-after-ibrutinib-treatment-for-relapsed-chronic-lymphocytic-leukemia
#11
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
https://www.readbyqxmd.com/read/29464716/richter-transformation-driven-by-epstein-barr-virus-reactivation-during-therapy-related-immunosuppression-in-chronic-lymphocytic-leukaemia
#12
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 leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV- tumours, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed 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 centre DLBCL phenotype, EBV latency programme type II or III, and very short survival...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29443760/resection-of-benign-side-branch-intraductal-papillary-mucinous-neoplasm-of-the-pancreas-is-long-term-follow-up-indicated-a-case-report-and-review-of-the-literature
#13
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)
https://www.readbyqxmd.com/read/29425341/fibroblast-growth-factor-23-is-induced-by-an-activated-renin-angiotensin-aldosterone-system-in-cardiac-myocytes-and-promotes-the-pro-fibrotic-crosstalk-between-cardiac-myocytes-and-fibroblasts
#14
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
https://www.readbyqxmd.com/read/29420244/chronic-lymphocytic-leukaemia-with-necrotic-herpetic-adenitis-an-elusive-clinical-condition
#15
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
https://www.readbyqxmd.com/read/29316456/disease-characteristics-and-clinical-outcomes-in-patients-aged-less-than-40-with-chronic-lymphocytic-leukemia
#16
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
https://www.readbyqxmd.com/read/29296799/near-tetraploidy-is-associated-with-richter-transformation-in-chronic-lymphocytic-leukemia-patients-receiving-ibrutinib
#17
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
https://www.readbyqxmd.com/read/29296715/clonal-evolution-underlying-leukemia-progression-and-richter-transformation-in-patients-with-ibrutinib-relapsed-cll
#18
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
https://www.readbyqxmd.com/read/29246803/venetoclax-for-chronic-lymphocytic-leukaemia-progressing-after-ibrutinib-an-interim-analysis-of-a-multicentre-open-label-phase-2-trial
#19
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...
January 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29235166/the-south-african-universal-preschool-year-a-case-study-of-policy-development-and-implementation
#20
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
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