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Ph+ acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28340183/crlf2-positive-b-cell-acute-lymphoblastic-leukemia-in-adult-patients-a-single-institution-experience
#1
Sergej Konoplev, Xinyan Lu, Marina Konopleva, Nitin Jain, Juan Ouyang, Maitrayee Goswami, Kathryn G Roberts, Marc Valentine, Charles G Mullighan, Carlos Bueso-Ramos, Patrick A Zweidler-McKay, Jeffrey L Jorgensen, Sa A Wang
Objectives: Cytokine receptor-like factor 2 ( CRLF2 ) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2 + cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%)...
March 13, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#2
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#3
Yihua E Ye, Caroline N Woodward, Narayana I Narasimhan
PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated. The objective of this phase 1, mass balance study was to evaluate the absorption, metabolism, and excretion of [(14)C]ponatinib in healthy subjects...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28140712/the-clinical-characteristics-and-prognostic-significance-of-aid-mir-181b-and-mir-155-expression-in-adult-patients-with-de-novo-b-cell-acute-lymphoblastic-leukemia
#4
Guangquan Zhou, Yang Cao, Weimin Dong, Yan Lin, Qi Wang, Wei Wu, Xiaoying Hua, Yun Ling, Xiaobao Xie, Shaoyan Hu, Jiannong Cen, Weiying Gu
This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28103625/phase-ii-study-of-imatinib-based-chemotherapy-for-newly-diagnosed-bcr-abl-positive-acute-lymphoblastic-leukemia
#5
Shin Fujisawa, Shuichi Mizuta, Hideki Akiyama, Yasunori Ueda, Yasutaka Aoyama, Yoshihiro Hatta, Kazuhiko Kakihana, Nobuaki Dobashi, Isamu Sugiura, Yasushi Onishi, Tomoya Maeda, Kiyotoshi Imai, Shigeki Ohtake, Yasushi Miyazaki, Kazunori Ohnishi, Keitaro Matsuo, Tomoki Naoe
This study investigated the efficacy of imatinib based therapy with intensified consolidation therapy in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to prevent early relapse. We conducted a phase II trial of imatinib-combined chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults. Sixty-eight patients were included in the trial between October 2008 and December 2010. The median age was 49 years, with 28 patients >55 years of age. Sixty-five patients achieved CR (95...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28050230/givinostat-a-type-ii-histone-deacetylase-inhibitor-induces-potent-caspase-dependent-apoptosis-in-human-lymphoblastic-leukemia
#6
Ying Li, Kevin Zhao, Chenjiao Yao, Samir Kahwash, Yan Tang, Guojiuan Zhang, Kara Patterson, Qi-En Wang, Weiqiang Zhao
Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28047771/su-g-tep3-07-on-the-development-of-mechano-biological-assessment-of-leukemia-cells-using-optical-tweezers
#7
E Brost, J Brooks, J Piepenburg, S Chakraborty, T Das, A Green, Y Watanabe, S Hui
PURPOSE: Patients with BCR-ABL (Ph +ve) acute lymphoblastic leukemia are at very high risk of relapse and mortality. In line with the NIH mission to understand the physical and biological processes, we seek to report mechano-biological method to assessment and distinguish treated/untreated leukemia cells. METHODS: BCR-ABL leukemia cell populations and silica microspheres were trapped in a 100x magnification optical trapping system (λ=660 nm, 70 mW). Light refracted through the trapped sample was collected in the back focal plane by a quadrant detector to measure the positions of individual cells...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28032081/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-8-years-experience-from-a-tertiary-care-center-in-india
#8
Madhav Danthala, Sadashivudu Gundeti, Laxmi Srinivas Maddali, Ashok Pillai, Krishna Chaitanya Puligundla, Raja Praveen Adusumilli
INTRODUCTION: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL...
October 2016: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28024477/-a-retrospective-study-of-ph-negative-adolescent-and-young-adults-with-acute-b-lymphoblastic-leukemia-in-two-centers
#9
Hong-Hao Gao, Yu Jing, Ming-Juan Liu, Hong-Hua Li, Wen-Rong Huang, Chun-Ji Gao, Dai-Hong Liu, Yong-Hui Li, Sai Huang, Yan Li, Jing Liu, Yong-Qing Zhang, Li Yu
OBJECTIVE: To analyze the therapeutic efficacy of different consolidation therapies after induction remission on Ph negative adolescent and young adults with acute B lymphoblastic leukemia, and to explore the effect of different risk factors on prognosis. METHODS: The treatment and efficacy of 80 Ph negative B-ALL in patients of 16-39 years old in the Hematology Department of 301(65 cases) and 309(15 cases) hospital from 1999 to 2016 are retrospectively analyzed...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#10
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/28002337/anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-two-case-reports
#11
Yang-Min Zhu, Zhao Wu, You-Ping Tan, Yuan-Yuan Du, Zhi Liu, Rui-Ming Ou, Shuang Liu, Cheng-Fei Pu, Jing Jiang, Jin-Ping Wang, Lei Xiao, Qing Zhang
RATIONALE: The presence of the Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (ALL) has been associated with a high risk of disease relapse and a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for adults with Ph-positive ALL, but relapse remains the primary cause of treatment failure, and is associated with an extremely poor prognosis. The emergence of resistance to tyrosine kinase inhibitors (TKIs) poses a challenge for patients with disease relapses after initial treatment with TKI-containing regimens...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27998202/second-cord-blood-transplantation-and-interferon-%C3%AE-maintenance-therapy-for-relapsed-ph-acute-lymphoblastic-leukemia-with-the-t315i-mutation
#12
Masahiko Sumi, Keijiro Sato, Hiroko Kaiume, Wataru Takeda, Takehiko Kirihara, Toshimitsu Ueki, Yuki Hiroshima, Hikaru Kobayashi
No abstract text is available yet for this article.
August 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27935576/acute-lymphoblastic-leukemia-relapsing-after-first-line-pediatric-inspired-therapy-a-retrospective-graall-study
#13
A Desjonquères, P Chevallier, X Thomas, F Huguet, T Leguay, M Bernard, J-O Bay, E Tavernier, A Charbonnier, F Isnard, M Hunault, P Turlure, M Renaud, J-N Bastié, C Himberlin, S Lepretre, B Lioure, V Lhéritier, V Asnafi, K Beldjord, M Lafage-Pochitaloff, M C Béné, N Ifrah, H Dombret
The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8...
December 9, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27932787/high-incidence-of-philadelphia-chromosome-like-acute-lymphoblastic-leukemia-in-older-adults-with-b-all
#14
S K Tasian, C Hurtz, G B Wertheim, N G Bailey, M S Lim, R C Harvey, I-M Chen, C L Willman, R Astles, A Zebrowski, S C Reshmi, M M Li, N V Frey, S M Luger, M Carroll, A E Perl
No abstract text is available yet for this article.
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#15
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
Although the emergence of bone marrow (BM)-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and using them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27919910/ph-like-acute-lymphoblastic-leukemia-a-high-risk-subtype-in-adults
#16
Nitin Jain, Kathryn G Roberts, Elias Jabbour, Keyur Patel, Agda Karina Eterovic, Ken Chen, Patrick Zweidler-McKay, Xinyan Lu, Gloria Fawcett, Sa A Wang, Sergej Konoplev, Richard C Harvey, I-Ming Chen, Debbie Payne-Turner, Marcus Valentine, Deborah Thomas, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Steven Kornblau, Susan O'Brien, Sherry Pierce, Jeffrey Jorgensen, Kenna R Mills Shaw, Cheryl L Willman, Charles G Mullighan, Hagop Kantarjian, Marina Konopleva
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are conflicting data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly diagnosed B-cell ALL (B-ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph(+), and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27913531/treatment-of-older-patients-with-acute-lymphoblastic-leukemia
#17
Nicola Gökbuget
The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913529/ph-like-acute-lymphoblastic-leukemia
#18
Thai Hoa Tran, Mignon L Loh
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a newly identified high-risk (HR) B-lineage ALL subtype, accounting for ∼15% of children with National Cancer Institute-defined HR B-ALL. It occurs more frequently in adolescents and adults, having been reported in as much as 27% of young adults with ALL between 21 and 39 years of age. It exhibits adverse clinical features, confers a poor prognosis, and harbors a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, making it amenable to treatment with tyrosine kinase inhibitor (TKI) therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#19
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894622/a-case-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-partial-trisomy-of-chromosome-1q-involving-chromosome-13-as-the-acceptor-a-novel-cytogenetic-finding
#20
Mohit Bharadwaj, Anurag Sharma, Rahul Katara, Dinesh Pradhan, Raman Arora, Reena Mittal, Sambit K Mohanty
The Philadelphia (Ph) chromosome is infrequently found in acute lymphoblastic leukemia and is associated with poor prognosis. We present a case of Ph chromosome positive B cell-acute lymphoblastic leukemia with the partial trisomy of chromosome 1q involving chromosome 13 as the acceptor which has never been reported in the English literature. Jumping translocation (JT) of chromosome 1 is rare and is associated with disease progression and poor prognosis. Herein, we report the first case of Ph chromosome positive B cell-acute lymphoblastic leukemia with coexisting jumping translocation of chromosome 1 leading to trisomy of chromosome 1q...
January 2017: Pathology, Research and Practice
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