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https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#1
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445187/the-effects-of-inherited-nudt15-polymorphisms-on-thiopurine-active-metabolites-in-japanese-children-with-acute-lymphoblastic-leukemia
#2
Takaya Moriyama, Rina Nishii, Ting-Nien Lin, Kentaro Kihira, Hidemi Toyoda, Nersting Jacob, Motohiro Kato, Katsuyoshi Koh, Hiroto Inaba, Atsushi Manabe, Kjeld Schmiegelow, Jun J Yang, Hiroki Hori
Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major genetic cause for MP-related bone marrow suppression, and there is increasing interest in the clinical implementation of NUDT15 genotype-guided MP dose individualization. Therefore, we sought to evaluate the effects of NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform NUDT15 genotype-guided MP dosing...
April 25, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28445014/detection-of-immunoglobulin-heavy-chain-gene-clonality-by-next-generation-sequencing-for-minimal-residual-disease-monitoring-in-b-lymphoblastic-leukemia
#3
Saeam Shin, In Sik Hwang, Jieun Kim, Kyung A Lee, Seung Tae Lee, Jong Rak Choi
Minimal residual disease (MRD) following B-lymphoblastic leukemia (B-ALL) treatment has gained prognostic importance. Clonal immunoglobulin heavy chain (IGH) gene rearrangement is a useful follow-up marker in B-ALL owing to its high positivity rate. We evaluated the performance and clinical applicability of a next-generation sequencing (NGS) assay for IGH rearrangement in B-ALL MRD monitoring. IGH rearrangement was tested by using fluorescence PCR-fragment analysis and the NGS assay in eight B-ALL patients...
July 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28444777/interphase-fish-for-bcr-abl1-rearrangement-on-neutrophils-a-decisive-tool-to-discriminate-a-lymphoid-blast-crisis-of-chronic-myeloid-leukemia-from-a-de-novo-bcr-abl1-positive-acute-lymphoblastic-leukemia
#4
Estelle Balducci, Marie Loosveld, Ilhem Rahal, John Boudjarane, Emilie Alazard, Chantal Missirian, Marina Lafage-Pochitaloff, Gérard Michel, Hélène Zattara
Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML...
April 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#5
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28444640/diagnostic-value-of-the-dual-luciferase-report-assay-for-predicting-response-to-glucocorticoid-in-children-with-acute-lymphoblastic-leukemia
#6
X Wang, P Chen, Y Sun, Y Chen, M Mao, T Jiang, J Ouyang
OBJECTIVE: Resistance to glucocorticoid (GC) is a significant clinical problem in some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC resistance are time consuming and have limited reproducibility; in this study, we sought to define a new method of evaluating GC sensitivity and resistance in vitro. METHODS: Based on the mechanisms of GC resistance, we hypothesized that the dual-luciferase report (DLR) assay could reflect the transcription effects of GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby allowing the evaluation of reactions to GC...
April 25, 2017: Clinical & Translational Oncology
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
#7
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/28443699/the-experiences-of-parents-of-pediatric-patients-with-acute-lymphoblastic-leukemia-2-months-after-completion-of-treatment
#8
Barbara Muskat, Heather Jones, Sonia Lucchetta, Wendy Shama, Sue Zupanec, Andrea Greenblatt
Diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) can be a highly stressful time for the entire family. While completion of treatment may bring relief to some families, it may also bring about additional anxieties and fear. The primary objective of this article is to present an analysis of the experiences, emotional states, and support needs of parents of pediatric cancer patients 2 months after treatment completion for ALL. Using a qualitative interpretive description approach, transcripts from interviews with 17 parents from the leukemia/lymphoma program of a large urban pediatric cancer center were analyzed using N-Vivo 10 data analysis software...
April 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#9
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/28440981/-leading-causes-of-death-during-the-induction-therapy-in-pediatric-patients-with-acute-lymphoblastic-leukemia
#10
Máximo Aguilar-Hernández, Gabriela Fernández-Castillo, Nora Nancy Núñez-Villegas, Ruy Xavier Pérez-Casillas, Juan Carlos Núñez-Enríquez
BACKGROUND: Leukemias are the leading cause of childhood cancer. In most developed countries 1-2% of patients die during remission induction; however, in developing countries, this figure is higher and the causes of death apparently vary among the populations studied. The aim was to determine the cause of death during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL) in the hospital "Dr. Gaudencio González Garza" of Centro Médico Nacional La Raza from January 1, 2009, to December 31, 2014...
May 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28440407/effects-of-cytochrome-p450-family-3-subfamily-a-member%C3%A2-5-gene-polymorphisms-on-daunorubicin-metabolism-and-adverse-reactions-in-patients-with-acute-leukemia
#11
Zhen Huang, Juxiang Wang, Jiangchao Qian, Yuan Li, Zhisheng Xu, Min Chen, Hongfei Tong
The present study aimed to investigate the association between the genetic polymorphism of cytochrome P450 family 3 subfamily A member 5 (CYP3A5) and the activity of CYP3A and plasma concentrations of daunorubicin (DNR) in patients with acute leukemia. A total of 36 children with newly diagnosed acute lymphoblastic leukemia were enrolled in the study. Polymerase chain reaction (PCR)‑restriction fragment length polymorphism and PCR product sequencing were used to detect the genotype of CYP3A5*3. PCR was then used to express the mRNA expression of CYP3A5...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440403/ginsenoside-rh2-and-rg3-inhibit-cell-proliferation-and-induce-apoptosis-by-increasing-mitochondrial-reactive-oxygen-species-in-human-leukemia-jurkat-cells
#12
Ting Xia, Ying-Nan Wang, Chuan-Xin Zhou, Li-Mei Wu, Yong Liu, Qian-Hong Zeng, Xiang-Long Zhang, Jia-Hui Yao, Min Wang, Jian-Pei Fang
Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell‑death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit‑8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP)...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440015/hypertriglyceridemia-during-asparaginase-treatment-in-children-with-acute-lymphoblastic-leukemia-correlates-with-antithrombin-activity-in-adolescents
#13
Lisa Persson, Arja Harila-Saari, Ida Hed Myrberg, Mats Heyman, Anna Nilsson, Susanna Ranta
BACKGROUND: Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent...
April 25, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28438676/factors-associated-with-long-term-risk-of-relapse-after-unrelated-cord-blood-transplantation-for-children-with-acute-lymphoblastic-leukemia-in-remission
#14
Kristin M Page, Myriam Labopin, Annalisa Ruggeri, Gerard Michel, Cristina Diaz de Heredia, Tracey O'Brien, Alessandra Picardi, Mouhab Ayas, Henrique Bittencourt, Ajay J Vora, Jesse Troy, Carmen Bonfim, Fernanda Volt, Eliane Gluckman, Peter Bader, Joanne Kurtzberg, Vanderson Rocha
For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared to other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GvHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence (CI) of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first (n=257, 40%) or second complete remission (CR; n=383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000-2012...
April 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28436979/successful-chimeric-ag-receptor-modified-t-cell-therapy-for-isolated-testicular-relapse-after-hematopoietic-cell-transplantation-in-an-acute-lymphoblastic-leukemia-patient
#15
J Yu, Y Hu, C Pu, Z Liang, Q Cui, H Zhang, Y Luo, J Shi, A Jin, L Xiao, Z Wu, H Huang
No abstract text is available yet for this article.
April 24, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28436581/pediatric-acute-lymphoblastic-leukemia-with-t-1-19-tcf3-pbx1-in-taiwan
#16
Hsiu-Ju Yen, Shih-Hsiang Chen, Tsung-Yen Chang, Chao-Ping Yang, Dong-Tsamn Lin, Iou-Jih Hung, Kai-Hsin Lin, Jiann-Shiuh Chen, Chih-Cheng Hsiao, Tai-Tsung Chang, Te-Kao Chang, Ching-Tien Peng, Ming-Tsan Lin, Tang-Her Jaing, Hsi-Che Liu, Shiann-Tarng Jou, Meng-Yao Lu, Chao-Neng Cheng, Jiunn-Ming Sheen, Shyh-Shin Chiou, Giun-Yi Hung, Kang-Hsi Wu, Ting-Chi Yeh, Shih-Chung Wang, Rong-Long Chen, Hsiu-Hao Chang, Yung-Li Yang, Shu-Huey Chen, Shin-Nan Cheng, Yu-Hsiang Chang, Bow-Wen Chen, Yuh-Lin Hsieh, Fang-Liang Huang, Wan-Ling Ho, Jinn-Li Wang, Chia-Yau Chang, Yu-Hua Chao, Pei-Chin Lin, Yu-Chieh Chen, Yu-Mei Liao, Tung-Huei Lin, Lee-Yung Shih, Der-Cherng Liang
BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28436558/adverse-effects-of-pegaspargase-in-pediatric-patients-receiving-doses-greater-than-3-750%C3%A2-iu
#17
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/28433605/stability-of-patient-specific-features-of-altered-dna-replication-timing-in-xenografts-of-primary-human-acute-lymphoblastic-leukemia
#18
Takayo Sasaki, Juan Carlos Rivera-Mulia, Daniel Vera, Jared Zimmerman, Sunny Das, Michelle Padget, Naoto Nakamichi, Bill H Chang, Jeff Tyner, Brian J Druker, Andrew P Weng, Curt I Civin, Connie J Eaves, David M Gilbert
Genome-wide DNA replication timing (RT) profiles reflect the global 3D chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of the cellular epigenetic state. Thus normal differentiation involves reproducible changes in RT and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro...
April 19, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28432946/design-and-synthesis-of-sulfonamide-substituted-diphenylpyrimidines-sfa-dppys-as-potent-bruton-s-tyrosine-kinase-btk-inhibitors-with-improved-activity-toward-b-cell-lymphoblastic-leukemia
#19
He Liu, Menghua Qu, Lina Xu, Xu Han, Changyuan Wang, Xiaohong Shu, Jihong Yao, Kexin Liu, Jinyong Peng, Yanxia Li, Xiaodong Ma
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430957/cd25-expression-in-b-lymphoblastic-leukemia-lymphoma-predicts-t-9-22-q34-q11-philadelphia-chromosome-translocation-ph-and-is-associated-with-residual-disease-in-ph-negative-patients
#20
Pu Chen, Andrew Chu, Hamid Zia, Prasad Koduru, Robert Collins, Naomi Winick, Franklin Fuda, Weina Chen
Objectives: CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia chromosome translocation (Ph); BCR-ABL1 rearrangement in B lymphoblastic leukemia/lymphoma (B-LL). However, the significance of CD25 expression in Ph negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is largely unknown. Methods: CD25 expression by flow cytometry (FC) was correlated with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29 marrow measured by FC in the context of cytogenetic risk stratification in Ph- patients...
November 1, 2016: American Journal of Clinical Pathology
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