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Adult Acute Leukemia

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https://www.readbyqxmd.com/read/28446270/-characteristics-and-clinical-significance-of-crlf2-mutations-in-adult-acute-lymphoblastic-leukemia
#1
Yan Gu, Yu-Jie Wu, Qi Han, Xi-Lian Zhou, Chun Qiao, Jian-Yong Li, Zheng Ge
OBJECTIVE: Cytokine receptor-like factor 2(CRLF2) plays an important role in the development of normal B lymphocytes, which can mediate early B cell proliferation and survival. The aim of this study was to investigate the mutations of CRLF2 and its clinical significance in adult patients with acute lymphoblastic leukemia(ALL). METHODS: Exons of CRLF2 were amplified, then the DNA was purified and sequenced; the frequency, position, types and clinical significance of CRLF2 mutations were analyzed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28444255/effect-of-cranial-irradiation-on-sperm-concentration-of-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-a-report-from-the-st-jude-lifetime-cohort-study%C3%A2
#2
Daniel M Green, Liang Zhu, Mingjuan Wang, Wassim Chemaitilly, DeoKumar Srivastava, William H Kutteh, Raymond W Ke, Charles A Sklar, Ching-Hon Pui, Larry E Kun, Raul C Ribeiro, Leslie L Robison, Melissa M Hudson
STUDY QUESTION: Does lower dose (<26 Gy) cranial radiation therapy (CRT) used for central nervous system prophylaxis in acute lymphoblastic leukemia (ALL) adversely affect sperm concentration or morphology? SUMMARY ANSWER: CRT doses <26 Gy had no demonstrable adverse effect on sperm concentration or morphology. WHAT IS KNOWN ALREADY: Treatment with alkylating agents produces oligospermia and azoospermia in some patients. No prior study has been large enough to evaluate the independent effects of alkylating agents and lower dose (<26 Gy) CRT on sperm concentration or morphology...
April 21, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#3
Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth, Eva-M Fehr, Sebastian Attig, Alexander Hohberger, Thomas Kindler, Jörg Faber
B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy...
April 24, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28440611/the-meningioma-1-mn1-gene-is-an-independent-poor-prognostic-factor-in-adult-egyptian-acute-myeloid-leukemia-patients
#4
Roxan E Shafik, Naglaa M Hassan, Yomna M El Meligui, Hanan E Shafik
Aim: To determine the prognostic importance of meningioma 1 (MN1) gene expression levels in the context of other predictive markers for acute myeloid leukemia (AML) cases. Methods: MN1 expression was measured in 85 newly diagnosed adults younger than 60 years by real-time reverse-transcriptase polymerase chain reaction. Results: At diagnosis 67.4% of cases had elevated MN1 expression, this being associated with a worse prognosis, higher incidence of lymphadenopathy and CD34 transcript expression (p=0.02 and <0...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28436558/adverse-effects-of-pegaspargase-in-pediatric-patients-receiving-doses-greater-than-3-750%C3%A2-iu
#5
Rachel Lebovic, Natalie Pearce, Laura Lacey, James Xenakis, Cassidy B Faircloth, Patrick Thompson
BACKGROUND: Increased toxicities have been identified with higher doses of pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28435324/symptomatic-central-nervous-system-involvement-in-adult-patients-with-acute-myeloid-leukemia
#6
Nael Alakel, Friedrich Stölzel, Brigitte Mohr, Michael Kramer, Uta Oelschlägel, Christoph Röllig, Martin Bornhäuser, Gerhard Ehninger, Markus Schaich
INTRODUCTION: Acute myeloid leukemia (AML) rarely involves the central nervous system (CNS). Little is known about the clinical course in adult AML patients since most studies examined pediatric patients. Therefore, this study analyzed the data of patients treated in three prospective trials of the "Study Alliance Leukemia" (SAL) study group for CNS involvement. METHODS: In all, 3,261 AML patients included in the prospective AML96, AML2003, and AML60+ trials of the SAL study group were analyzed...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28434262/the-emergence-of-acid-ceramidase-as-a-therapeutic-target-for-acute-myeloid-leukemia
#7
Su-Fern Tan, Jennifer M Pearson, David J Feith, Thomas P Loughran
Acute myeloid leukemia (AML) is the most common adult leukemia. Only a fraction of AML patients will survive with existing chemotherapy regimens. Hence, there is an urgent and unmet need to identify novel targets and develop better therapeutics in AML. In the past decade, the field of sphingolipid metabolism has emerged into the forefront of cancer biology due to its importance in cancer cell proliferation and survival. In particular, acid ceramidase (AC) has emerged as a promising therapeutic target due to its role in neutralizing the pro-death effects of ceramide...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28428987/microarray-profiling-and-co-expression-network-analysis-of-the-lncrnas-and-mrnas-associated-with-acute-leukemia-in-adults
#8
Hui Cheng, Chong Mei Huang, Yang Wang, Xiao Xia Hu, Xiao Qian Xu, Xian Min Song, Gu Sheng Tang, Li Chen, Jian Min Yang
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#9
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28426850/second-primary-malignant-neoplasms-and-survival-in-adolescent-and-young-adult-cancer-survivors
#10
Theresa H M Keegan, Archie Bleyer, Aaron S Rosenberg, Qian Li, Melanie Goldfarb
Importance: Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age. Objective: To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (≥40 years) patients with the same SPMs...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28420034/a-fluorescence-in-situ-hybridization-based-screen-allows-rapid-detection-of-adverse-cytogenetic-alterations-in-patients-with-acute-myeloid-leukemia
#11
Nadine Sandhöfer, Klaus H Metzeler, Purvi M Kakadia, Zlatana Pasalic, Wolfgang Hiddemann, Michaela Neusser, Ortrud Steinlein, Michael Fiegl, Marion Subklewe, Karsten Spiekermann, Stefan K Bohlander, Stephanie Schneider, Jan Braess
In adult acute myeloid leukemia (AML), the karyotype of the leukemic cell is among the strongest prognostic factors. The Medical Research Council (MRC) and the European LeukemiaNet (ELN) classifications distinguish between favorable, intermediate and adverse cytogenetic risk patients who differ in their treatment response and overall survival. Conventional cytogenetic analyses are a mandatory component of AML diagnostics but they are time-consuming; therefore, therapeutic decisions in elderly patients are often delayed...
April 18, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28419558/age-but-not-philadelphia-positivity-impairs-outcome-in-older-elderly-patients-with-acute-lymphoblastic-leukemia-in-sweden
#12
Piotr Kozlowski, Emma Lennmyr, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Holger Karbach, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Heléne Hallböök
OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype...
April 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28419486/population-pharmacokinetic-analysis-of-bortezomib-in-pediatric-leukemia-patients-model-based-support-for-body-surface-area-based-dosing-over-the-2-to-16-year-age-range
#13
Michael J Hanley, Diane R Mould, Timothy J Taylor, Neeraj Gupta, Kaveri Suryanarayan, Rachel Neuwirth, Dixie-Lee Esseltine, Terzah M Horton, Richard Aplenc, Todd A Alonzo, Xiaomin Lu, Ashley Milton, Karthik Venkatakrishnan
This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28418922/novel-impact-of-the-dnmt3a-r882h-mutation-on-gsh-metabolism-in-a-k562-cell-model-established-by-talens
#14
Li Yang, Ya'Nan Liu, Na Zhang, Xiao'Yi Ding, Wei Zhang, Ke'Feng Shen, Liang Huang, Jian'Feng Zhou, Sen Cui, Zun'Min Zhu, Zheng Hu, Min Xiao
DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417551/morbidity-and-mortality-after-treatment-of-ewing-sarcoma-a-single-institution-experience
#15
Danielle Novetsky Friedman, Katherine Chastain, Joanne F Chou, Chaya S Moskowitz, Roberto Adsuar, Leonard H Wexler, Alexander J Chou, Amelia DeRosa, Joanne Candela, Heather Magnan, Shawn Pun, Tamara Kahan, Suzanne L Wolden, Paul A Meyers, Kevin C Oeffinger
BACKGROUND: Children, adolescents, and young adults treated for Ewing sarcoma (ES) are at risk for disease-related and treatment-related complications. We aimed to describe early and late overall mortality, cause-specific mortality, and key adverse health outcomes in a large, single-institutional cohort of patients with ES. METHODS: Patients with ES diagnosed at age less than 40 years and treated at Memorial Sloan Kettering between 1974 and 2012 were included. Overall survival was estimated using Kaplan-Meier methods...
April 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28415593/cysteine-and-glycine-rich-protein-2-csrp2-transcript-levels-correlate-with-leukemia-relapse-and-leukemia-free-survival-in-adults-with-b-cell-acute-lymphoblastic-leukemia-and-normal-cytogenetics
#16
Shu-Juan Wang, Ping-Zhang Wang, Robert Peter Gale, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Hui Zhang, Bin Jiang, Lan-Ping Xu, Xiao-Jun Huang, Kai-Yan Liu, Guo-Rui Ruan
Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#17
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28412288/adult-t-type-lymphoblastic-lymphoma-treatment-advances-and-prognostic-indicators
#18
REVIEW
Stéphane Lepretre, Carlos Graux, Aurore Touzart, Elizabeth Macintyre, Nicolas Boissel
T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. In this review, we describe the treatment of adult T-LBL with a focus on recent advances using pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly improved outcome. We also discuss the development of prognostic indicators for T-LBL, especially oncogenetic factors, that can identify patients at higher risk of relapse and should help further extend T-LBL patient survival...
April 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28411378/immune-responses-and-long-term-disease-recurrence-status-after-telomerase-based-dendritic-cell-immunotherapy-in-patients-with-acute-myeloid-leukemia
#19
Hanna J Khoury, Robert H Collins, William Blum, Patrick S Stiff, Laurence Elias, Jane S Lebkowski, Anita Reddy, Kevin P Nishimoto, Debasish Sen, Edward D Wirth, Casey C Case, John F DiPersio
BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved...
April 14, 2017: Cancer
https://www.readbyqxmd.com/read/28410228/identification-of-a-novel-functional-jak1-s646p-mutation-in-acute-lymphoblastic-leukemia
#20
Qian Li, Botao Li, Liangding Hu, Hongmei Ning, Min Jiang, Danhong Wang, Tingting Liu, Bin Zhang, Hu Chen
The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice...
March 29, 2017: Oncotarget
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