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Relapsed acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29464016/inhibition-of-the-nedd8-conjugation-pathway-induces-calcium-dependent-compensatory-activation-of-the-pro-survival-mek-erk-pathway-in-acute-lymphoblastic-leukemia
#1
Shuhua Zheng, Gilles M Leclerc, Bin Li, Ronan T Swords, Julio C Barredo
De novo and acquired drug resistance and subsequent relapse remain major challenges in acute lymphoblastic leukemia (ALL). We previously identified that pevonedistat (TAK-924, MLN4924), a first-in-class inhibitor of NEDD8 activating enzyme (NAE), elicits ER stress and has potent in vitro and in vivo efficacy against ALL. However, in pevonedistat-treated ALL cell lines, we found consistent activation of the pro-survival MEK/ERK pathway, which has been associated with relapse and poor outcome in ALL. We uncovered that inhibition of the MEK/ERK pathway in vitro and in vivo sensitized ALL cells to pevonedistat...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29458388/a-novel-generation-1928zt2-car-t-cells-induce-remission-in-extramedullary-relapse-of-acute-lymphoblastic-leukemia
#2
Jianyu Weng, Peilong Lai, Le Qin, Yunxin Lai, Zhiwu Jiang, Chenwei Luo, Xin Huang, Suijing Wu, Dan Shao, Chengxin Deng, Lisi Huang, Zesheng Lu, Maohua Zhou, Lingji Zeng, Dongmei Chen, Yulian Wang, Xiaomei Chen, Suxia Geng, Weinkove Robert, Zhaoyang Tang, Chang He, Peng Li, Xin Du
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its efficacy in B-ALL patients with extramedullary involvement is limited due to poor responses and neurotoxicity. Here, we utilized a third generation of CAR T cell vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with extramedullary involvement...
February 20, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29455318/expression-of-terminal-deoxynucleotidyl-transferase-tdt-in-classical-seminoma-a-potential-diagnostic-pitfall
#3
Alexander Brobeil, Florian Wagenlehner, Stefan Gattenlöhner
Seminomas are the most frequent testicular tumors and in spite of specific markers some histological subtypes can be diagnostically challenging due to the potential overlap of morphologic features and a variant antigen expression. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in hematogones, thymic T cells, lymphoblastic lymphoma/leukemia (LBL), and in some cases of acute myeloid leukemia but so far has not been described to be expressed in seminomas. After observing a reactivity of TdT in one case of seminoma, we analyzed ten additional tumors by immunohistochemistry to determine their spectrum of reactivity for TdT...
February 18, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29451276/tisagenlecleucel-an-approved-anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-leukemia
#4
Y Liu, X Chen, W Han, Y Zhang
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients. Conventional standard therapies for B-ALL have high failure rates, thus developing new therapies is crucial for patients with B-ALL...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29449681/secondary-philadelphia-chromosome-acquired-during-therapy-of-acute-leukemia-and-myelodysplastic-syndrome
#5
Habibe Kurt, Lan Zheng, Hagop M Kantarjian, Guilin Tang, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zimu Gong, Hesham M Amin, Sergej N Konoplev, Mark J Routbort, Xin Han, Wei Wang, L Jeffery Medeiros, Shimin Hu
The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis...
February 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29449434/msh6-haploinsufficiency-at-relapse-contributes-to-the-development-of-thiopurine-resistance-in-pediatric-b-lymphoblastic-leukemia
#6
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29442287/recent-developments-in-adolescent-and-young-adult-aya-acute-lymphoblastic-leukemia
#7
REVIEW
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
February 14, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29438091/a-phase-i-dose-escalation-study-of-clofarabine-in-patients-with-relapsed-or-refractory-low-grade-or-intermediate-grade-b-cell-or-t-cell-lymphoma
#8
Francine Marie Foss, Terri Parker
LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...
February 7, 2018: Oncologist
https://www.readbyqxmd.com/read/29434969/a-unique-bone-marrow-lymphoma-patient-presenting-with-an-isolated-mass-a-case-report
#9
Yi-Wen Xu, Ming-Hui Duan
Bone marrow lymphoma with the onset of an isolated mass in the bone marrow is extremely rare. The present case report described a unique case of B cell lymphoblastic lymphoma (LBL) presenting with an isolated mass in the bone marrow cavity, without any organopathy or lymphadenopathy. An isolated mass in bone marrow is a rare primary manifestation of LBL. The patient in the present case report presented with pain in the right elbow, a fever, pancytopenia and splenomegaly. Additionally, no abnormality was determined in the lymph nodes, the bone marrow karyotype or a computed tomography scan of the humerus...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434963/a-rare-e14a3-bcr-abl-fusion-transcript-in-acute-lymphoblastic-leukemia-patient-treated-with-car-modified-t-cell-therapy
#10
Haodong Cai, Li Yang, Kefeng Shen, Wei Zhang, Jie Xiong, Meilan Zhang, Xia Mao, Ying Wang, Min Xiao
E14a3 breakpoint cluster region (BCR)/ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL) fusion transcript is rare in Philadelphia chromosome positive disease, particularly in acute lymphoblastic leukemia (ALL). Recently an e14a3 fusion transcript was detected by multiple laboratory examinations, and the patient was suffering from ALL. Except for the BCR/ABL fusion gene, in the present study the patient additionally had an IKAROS family zinc finger 1 deletion which, has been confirmed as a significant adverse prognosis factor...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434033/-pdgfrb-mutation-and-tyrosine-kinase-inhibitor-resistance-in-ph-like-acute-lymphoblastic-leukemia
#11
Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Aleš Hnízda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J Yang, Xiaofan Zhu, Xin Liu
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) comprises of approximately 10-15% of childhood ALL cases, many of whom respond exquisitely to tyrosine kinase inhibitors (TKIs), e.g., imatinib in PDGFRB -rearranged ALL. However, some cases developed drug resistance to TKIs with mechanisms poorly understood. In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB , and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation PDGFRBC843G , which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib...
February 6, 2018: Blood
https://www.readbyqxmd.com/read/29429020/leukemia-propagating-cells-demonstrate-distinctive-gene-expression-profiles-compared-with-other-cell-fractions-from-patients-with-de-novo-philadelphia-chromosome-positive-all
#12
Hong-Yan Zhao, Yang Song, Xie-Na Cao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Yuan Kong
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph + ALL. Using a xenograft assay, LPCs enrichment in the CD34 + CD38 - CD58 - fraction in Ph + ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph + ALL...
February 10, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29425516/reprint-of-building-a-safer-and-faster-car-seatbelts-airbags-and-crispr
#13
REVIEW
Miguel-Angel Perales, Partow Kebriaei, Leslie S Kean, Michel Sadelain
Therapeutic T cell engineering has recently garnered widespread interest because of the success of CD19 chimeric antigen receptor (CAR) therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma...
March 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29423088/identification-of-survivin-as-a-promising-target-for-the-immunotherapy-of-adult-b-cell-acute-lymphoblastic-leukemia
#14
Laurie Freire Boullosa, Payalben Savaliya, Stephanie Bonney, Laurence Orchard, Hannah Wickenden, Cindy Lee, Evelien Smits, Alison H Banham, Ken I Mills, Kim Orchard, Barbara-Ann Guinn
B-cell acute lymphoblastic leukemia (B-ALL) is a rare heterogeneous disease characterized by a block in lymphoid differentiation and a rapid clonal expansion of immature, non-functioning B cells. Adult B-ALL patients have a poor prognosis with less than 50% chance of survival after five years and a high relapse rate after allogeneic haematopoietic stem cell transplantation. Novel treatment approaches are required to improve the outcome for patients and the identification of B-ALL specific antigens are essential for the development of targeted immunotherapeutic treatments...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29419426/heterozygous-carriers-of-germline-c-657_661del5-founder-mutation-in-nbn-gene-are-at-risk-of-central-nervous-system-relapse-of-b-cell-precursor-acute-lymphoblastic-leukemia
#15
Bartlomiej Tomasik, Agata Pastorczak, Wojciech Fendler, Marcin Bartlomiejczyk, Marcin Braun, Marcin Mycko, Joanna Madzio, Ewa Polakowska, Edyta Ulińska, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Bernarda Kazanowska, Tomasz Szczepański, Jan Styczyński, Nina Irga-Jaworska, Wojciech Młynarski
No abstract text is available yet for this article.
February 1, 2018: Haematologica
https://www.readbyqxmd.com/read/29417201/cd19-targeted-car-t-therapy-versus-chemotherapy-in-re-induction-treatment-of-refractory-relapsed-acute-lymphoblastic-leukemia-results-of-a-case-controlled-study
#16
Guoqing Wei, Yongxian Hu, Chengfei Pu, Jian Yu, Yi Luo, Jimin Shi, Qu Cui, Wenjun Wu, Jinping Wang, Lei Xiao, Zhao Wu, He Huang
Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated...
February 7, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29416770/hprt1-activity-loss-is-associated-with-resistance-to-thiopurine-in-all
#17
Fan Yang, Houshun Fang, Dan Wang, Yao Chen, Yonggong Zhai, Bin-Bing S Zhou, Hui Li
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro, we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415942/-initial-presentation-of-lymphoblastic-crisis-in-a-pediatric-chronic-myelogenous-leukemia-patient
#18
Kosuke Akiyama, Shohei Yamamoto, Yumiko Sugishita, Ryota Kaneko, Naoko Okamoto, Masaya Koganesawa, Sachio Fujita, Ryosuke Matsuno, Daisuke Toyama, Keiichi Isoyama
A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29411126/febrile-events-in-acute-lymphoblastic-leukemia-a-prospective-observational-multicentric-seifem-study-seifem-2012-b-all
#19
Roberta Di Blasi, Chiara Cattaneo, Russell E Lewis, Mario Tumbarello, Laura Angelici, Giulia Dragonetti, Alessandro Busca, Benedetta Cambò, Anna Candoni, Monica Cesarini, Simone Cesaro, Mario Delia, Rosa Fanci, Francesca Farina, Mariagrazia Garzia, Antonio Giordano, Bruno Martino, Lorella Melillo, Gianpaolo Nadali, Vincenzo Perriello, Marco Picardi, Angela Maria Quinto, Prassede Salutari, Angelica Spolzino, Adriana Vacca, Calogero Vetro, Michelle Zancanella, Annamaria Nosari, Franco Aversa, Livio Pagano
The purpose of the present study is to estimate the current incidence of febrile events (FEs) and infectious episodes in acute lymphoblastic leukemia (ALL) and evaluate the outcome. We analyzed data on all FEs in a cohort of patients affected by ALL admitted to 20 Italian hematologic centers during 21 months of observation from April 1, 2012 to December 31, 2013. Data about treatment phase, steroids, neutropenia, type and site of infection, and outcome of infection were collected. The population comprehended 271 ALL adult patients...
February 7, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29408328/ribociclib-a-cdk4-cdk6-kinase-inhibitor-enhances-glucocorticoid-sensitivity-in-b-acute-lymphoblastic-leukemia-b-all
#20
Roberta Bortolozzi, Elena Mattiuzzo, Luca Trentin, Benedetta Accordi, Giuseppe Basso, Giampietro Viola
Dysregulation of the cyclin D1-CDK4/CDK6 complex is frequently observed in almost all human cancer and contributes to aberrant cell proliferation and consequent tumorigenesis. Although many reports described the importance of CDK4/CDK6 in different set of human tumors, only few studies have been performed on leukemia. By gene expression analysis performed in a cohort of childhood patients affected by B-acute lymphoblastic leukemia (B-ALL) we found that both CDK4 and CDK6 are highly expressed. Moreover, Reverse Phase Protein Array (RPPA) analysis showed that cyclin D1 levels are higher in patients undergoing relapse...
February 3, 2018: Biochemical Pharmacology
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