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Richters transformation

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https://www.readbyqxmd.com/read/28489849/utilizing-bmp-2-muteins-for-treatment-of-multiple-myeloma
#1
Axel Seher, Charlotte Lagler, Thorsten Stühmer, Urs Dietmar Achim Müller-Richter, Alexander Christian Kübler, Walter Sebald, Thomas Dieter Müller, Joachim Nickel
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM...
2017: PloS One
https://www.readbyqxmd.com/read/28473414/large-b-cell-lymphoma-variant-of-richter-transformation-originates-in-pseudoproliferation-centers-of-small-lymphocytic-lymphoma
#2
https://www.readbyqxmd.com/read/28473407/clinico-pathological-features-and-outcomes-of-progression-of-cll-on-the-bcl2-inhibitor-venetoclax
#3
Mary Ann Anderson, Constantine Tam, Thomas E Lew, Surender Juneja, Manu Juneja, David Westerman, Meaghan Wall, Stephen Lade, Alexandra Gorelik, David C S Huang, John F Seymour, Andrew W Roberts
The BCL2 inhibitor venetoclax achieves responses in ~79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemo-immunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinico-pathological features of PD and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pre-treated patients on three early phase clinical trials...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28468797/selective-inhibition-of-nuclear-export-with-selinexor-in-patients-with-non-hodgkin-s-lymphoma
#4
John Kuruvilla, Michael Savona, Rachid Baz, Morten Mau-Sorensen, Nashat Gabrail, Ramiro Garzon, Richard Stone, Michael Wang, Lynn Savoie, Peter Martin, Ian Flinn, Meagan Jacoby, T J Unger, Jean R Saint-Martin, Tami Rashal, Sharon Friedlander, Robert Carlson, Michael Kauffman, Sharon Shacham, Martin Gutierrez
Patients with relapsed or refractory (R/R) non-Hodgkin's lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B cell lymphoma (DLBCL), Richter's transformation, mantle cell lymphoma (MCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) were enrolled...
May 3, 2017: Blood
https://www.readbyqxmd.com/read/28450576/de-novo-richter-transformation
#5
Laura Chiecchio, Jonathan Oliver Cullis
No abstract text is available yet for this article.
April 27, 2017: Blood
https://www.readbyqxmd.com/read/28447755/gene-expression-profile-in-human-induced-pluripotent-stem-cells-chondrogenic-differentiation-in-vitro-part-a
#6
Wiktoria Maria Suchorska, Ewelina Augustyniak, Magdalena Richter, Tomasz Trzeciak
Human induced pluripotent stem cells (hiPSCs) offer promise in regenerative medicine, however more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte‑like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with HC‑402‑05a cells or supplemented with transforming growth factor β3 (TGF‑β3), and to assess the relative utility of the most commonly used chondrogenic markers as indicators of cell differentiation...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447733/gene-expression-profile-in-human-induced-pluripotent-stem-cells-chondrogenic-differentiation-in%C3%A2-vitro-part-b
#7
Ewelina Augustyniak, Wiktoria Maria Suchorska, Tomasz Trzeciak, Magdalena Richter
The development of human induced pluripotent stem cells (hiPSCs) is considered a turning point in tissue engineering. However, more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte‑like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic‑like cells derived from hiPSCs cultured in mediums conditioned with HC‑402‑05a cells or supplemented with transforming growth factor β3 (TGF‑β3), and to assess the relative utility of the most commonly‑used chondrogenic markers as indicators of cell differentiation...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#8
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28424162/pembrolizumab-in-patients-with-chronic-lymphocytic-leukemia-with-richter-s-transformation-and-relapsed-cll
#9
Wei Ding, Betsy R LaPlant, Timothy G Call, Sameer A Parikh, Jose F Leis, Rong He, Tait D Shanafelt, Sutapa Sinha, Jennifer Le-Rademacher, Andrew L Feldman, Thomas M Habermann, Thomas E Witzig, Gregory A Wiseman, Yi Lin, Erik Asmus, Grzegorz S Nowakowski, Michael J Conte, Deborah A Bowen, Casey N Aitken, Daniel L Van Dyke, Patricia T Greipp, Xin Liu, Xiaosheng Wu, Henan Zhang, Charla R Secreto, Shulan Tian, Esteban Braggio, Linda E Wellik, Ivana Micallef, David S Viswanatha, Huihuang Yan, Asher A Chanan-Khan, Neil E Kay, Haidong Dong, Stephen M Ansell
CLL patients progressed early on ibrutinib often develop Richter's transformation (RT) with short survival about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study MC1485 (NCT02332980) was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled and 60% received prior ibrutinib...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28340951/epstein-barr-virus-hemophagocytic-lymphohistiocytosis-related-to-rituximab-use-and-immunopathogenetic-insights
#10
Sotirios G Papageorgiou, Sotirios Tsiodras, Georgios Siakallis, Efthimia Bazani, Aris Spathis, Garyfalia Poulakou, Penelope Korkolopoulou, Ioannis Panayiotides, Vasiliki Pappa
Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation. Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed...
December 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28295527/factors-predicting-survival-in-chronic-lymphocytic-leukemia-patients-developing-richter-syndrome-transformation-into-hodgkin-lymphoma
#11
Francesca Romana Mauro, Piero Galieni, Alessandra Tedeschi, Luca Laurenti, Giovanni Del Poeta, Gianluigi Reda, Marina Motta, Alessandro Gozzetti, Roberta Murru, Maria Denise Caputo, Melissa Campanelli, Anna Maria Frustaci, Idanna Innocenti, Sara Raponi, Anna Guarini, Fortunato Morabito, Robin Foà, Massimo Gentile
We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%...
March 10, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28228478/an-engineered-transforming-growth-factor-%C3%AE-tgf-%C3%AE-monomer-that-functions-as-a-dominant-negative-to-block-tgf-%C3%AE-signaling
#12
Sun Kyung Kim, Lindsey Barron, Cynthia S Hinck, Elyse M Petrunak, Kristin E Cano, Avinash Thangirala, Brian Iskra, Molly Brothers, Machell Vonberg, Belinda Leal, Blair Richter, Ravindra Kodali, Alexander B Taylor, Shoucheng Du, Christopher O Barnes, Traian Sulea, Guillermo Calero, P John Hart, Matthew J Hart, Borries Demeler, Andrew P Hinck
The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28218627/gata4-dependent-organ-specific-endothelial-differentiation-controls-liver-development-and-embryonic-hematopoiesis
#13
Cyrill Géraud, Philipp-Sebastian Koch, Johanna Zierow, Kay Klapproth, Katrin Busch, Victor Olsavszky, Thomas Leibing, Alexandra Demory, Friederike Ulbrich, Miriam Diett, Sandhya Singh, Carsten Sticht, Katja Breitkopf-Heinlein, Karsten Richter, Sanna-Maria Karppinen, Taina Pihlajaniemi, Bernd Arnold, Hans-Reimer Rodewald, Hellmut G Augustin, Kai Schledzewski, Sergij Goerdt
Microvascular endothelial cells (ECs) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular ECs instruct neighboring cells in their organ-specific vascular niches through angiocrine factors, which include secreted growth factors (angiokines), extracellular matrix molecules, and transmembrane proteins. However, the molecular regulators that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity are largely elusive. In contrast to other ECs, which form a continuous cell layer, liver sinusoidal ECs (LSECs) constitute discontinuous, permeable microvessels...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218069/concomitant-presence-of-cd5-positive-diffuse-large-b-lymphoma-and-monoclonal-b-cells-with-cll-immunophenotype-is-it-richter-s-transformation
#14
Sabina Langer, Jasmita Dass, Suchi Mittal, Shyam Aggarwal
No abstract text is available yet for this article.
February 20, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28203174/richter-s-syndrome-with-hypercalcemia-induced-by-tumor-associated-production-of-parathyroid-hormone-related-peptide
#15
Naoki Watanabe, Hajime Yasuda, Soji Morishita, Yasuo Aota, Junichi Tomomatsu, Masaru Tanaka, Akimichi Ohsaka, Norio Komatsu
Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28191372/richter-transformation-of-chronic-lymphocytic-leukemia-a-review-of-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-and-molecular-diagnostics
#16
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/28171709/long-term-outcomes-for-patients-with-chronic-lymphocytic-leukemia-who-discontinue-ibrutinib
#17
Preetesh Jain, Philip A Thompson, Michael Keating, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Hagop Kantarjian, Jan A Burger, Susan O'Brien, William G Wierda
BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. METHODS: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#18
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
March 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28067096/differential-response-of-normal-and-transformed-mammary-epithelial-cells-to-combined-treatment-of-anti-mir-21-and-radiation
#19
Vanja Radulovic, Theresa Heider, Sabine Richter, Simone Moertl, Michael J Atkinson, Nataša Anastasov
PURPOSE: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation. MATERIALS AND METHODS: The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach...
January 9, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27905140/herpes-simplex-infection-simulating-richter-transformation-a-series-of-four-cases-and-review-of-the-literature
#20
Alireza Salem, Sanam Loghavi, Joseph D Khoury, Rose Lou Marie C Agbay, Jeffrey L Jorgensen, L Jeffrey Medeiros
AIMS: Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), and is associated with a poor outcome. The histological manifestations of RT are variable, and include an increase in the proportion of prolymphocytes, immunoblasts, and other pleomorphic cells, along with an increased proliferation rate and often necrosis. Rarely, superimposed herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically...
April 2017: Histopathology
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