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acute lymphoblastic

Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Yimei Ma, Xizhou An, Xianmin Guan, Qinglin Kong, Yanzhen Wang, Pengfei Li, Yan Meng, Yinghui Cui, Xianhao Wen, Yuxia Guo, Yali Shen, Jie Yu
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis...
April 2018: Oncology Letters
Amara Gul, Sadia Zafar
The objective of the current study was to compare cognitive flexibility and emotion regulation between childhood survivors of Acute Lymphoblastic Leukaemia (ALL) and healthy control subjects. Twenty-five childhood survivors of ALL treated with intrathecal chemotherapy between 2013 to 2016 from Shaukat Khanum Memorial Cancer Hospital, Children Hospital and Jinnah Hospital Lahore and twenty-five healthy demographically matched children (control group) participated in the study. Participants performed task switching experiment as a measure of cognitive flexibility and emotion regulation questionnaire for children and adolescents...
March 2018: JPMA. the Journal of the Pakistan Medical Association
Lisa M Ebert, Wenbo Yu, Tessa Gargett, Michael P Brown
Chimeric antigen receptor (CAR)-T cell therapy has been clinically validated as a curative treatment for the difficult to treat malignancies of relapsed/refractory B-cell acute lymphoblastic leukaemia and lymphoma. Here, the CAR-T cells are re-directed towards a single antigen, CD19, which is recognised as a virtually ideal CAR target antigen because it has strong, uniform expression on cancer cells, and is otherwise expressed only on healthy B cells, which are 'dispensable'. Notwithstanding the clinical success of CD19-CAR-T cell therapy, its single specificity has driven therapeutic resistance in 30% or more of cases with CD19-negative leukaemic relapses...
March 14, 2018: Biochemical Society Transactions
Heng Xu, Yang Shu
Treatment outcomes for acute lymphoblastic leukemia (ALL), especially pediatric ALL, have greatly improved due to the risk-adapted therapy. Combination of drug development, clinical practice, as well as basic genetic researches has brought the survival rate of ALL from less than 10% to more than 90% today, not only increasing the treatment efficacy but also limiting adverse drug reactions (ADRs). In this review, we summarized the landscape identification of ALL genetic alterations, which provided the opportunity to increase the survival rate and especially minimize the relapse risk of ALL, and highlighted the importance of the development of new technologies of genomic investigation for translational medicine...
2018: Methods in Molecular Biology
Aleš Hnízda, Milan Fábry, Takaya Moriyama, Petr Pachl, Michael Kugler, Vítězslav Brinsa, David B Ascher, William L Carroll, Petr Novák, Markéta Žaliová, Jan Trka, Pavlína Řezáčová, Jun J Yang, Václav Veverka
Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sarah D Cramer, Julie A Hixon, Caroline Andrews, Ross J Porter, Gisele O L Rodrigues, Xiaolin Wu, Tim Back, Kelli Czarra, Helen Michael, Maggie Cam, Jack Chen, Dominic Esposito, Emilee Senkevitch, Vijay Negi, Peter D Aplan, Wenqing Li, Scott K Durum
No abstract text is available yet for this article.
February 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Elva Jiménez-Hernández, Arturo Fajardo-Gutiérrez, Juan Carlos Núñez-Enriquez, Jorge Alfonso Martín-Trejo, Laura Eugenia Espinoza-Hernández, Janet Flores-Lujano, José Arellano-Galindo, Aurora Medina-Sanson, Rogelio Paredes-Aguilera, Laura Elizabeth Merino-Pasaye, Martha Margarita Velázquez-Aviña, José Refugio Torres-Nava, Rosa Martha Espinosa-Elizondo, Raquel Amador-Sánchez, Juan José Dosta-Herrera, Javier Anastacio Mondragón-García, Heriberto Valdés-Guzmán, Laura Mejía-Pérez, Gilberto Espinoza-Anrubio, María Minerva Paz-Bribiesca, Perla Salcedo-Lozada, Rodolfo Ángel Landa-García, Rosario Ramírez-Colorado, Luis Hernández-Mora, María Luisa Pérez-Saldivar, Marlene Santamaría-Ascencio, Anselmo López-Loyola, Arturo Hermilo Godoy-Esquivel, Luis Ramiro García-López, Alison Ireri Anguiano-Ávalos, Karina Mora-Rico, Alejandro Castañeda-Echevarría, Roberto Rodríguez-Jiménez, José Alberto Cibrian-Cruz, Karina Anastacia Solís-Labastida, Rocío Cárdenas-Cardos, Armando Martínez-Avalos, Luz Victoria Flores-Villegas, José Gabriel Peñaloza-González, Ana Itamar González-Ávila, Martha Beatriz Altamirano-García, Norma López-Santiago, Martin Sánchez-Ruiz, Roberto Rivera-Luna, Luis Rodolfo Rodríguez-Villalobos, Francisco Hernández-Pérez, Jaime Ángel Olvera-Durán, Luis Rey García-Cortés, Minerva Mata-Rocha, Omar Alejandro Sepúlveda-Robles, Cesar Raúl González-Bonilla, Vilma Carolina Bekker-Méndez, Silvia Jiménez-Morales, Haydee Rosas-Vargas, Juan Manuel Mejía-Aranguré
In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015...
March 13, 2018: Cancer Medicine
Barbara J McClure, Susan L Heatley, Chung H Kok, Teresa Sadras, Jiyuan An, Timothy P Hughes, Richard B Lock, David Yeung, Rosemary Sutton, Deborah L White
BACKGROUND: Zinc-finger protein 384 (ZNF384) fusions are an emerging subtype of precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL) and here we further characterised their prevalence, survival outcomes and transcriptome. METHODS: Bone marrow mononuclear cells from 274 BCR-ABL1-negative pre-B-ALL patients were immunophenotyped and transcriptome molecularly characterised. Transcriptomic data was analysed by principal component analysis and gene-set enrichment analysis to identify gene and pathway expression changes...
March 13, 2018: British Journal of Cancer
Łukasz Sędek, Prisca Theunissen, Elaine Sobral da Costa, Alita van der Sluijs-Gelling, Ester Mejstrikova, Giuseppe Gaipa, Alicja Sonsala, Magdalena Twardoch, Elen Oliveira, Michaela Novakova, Chiara Buracchi, Jacques J M van Dongen, Alberto Orfao, Vincent H J van der Velden, Tomasz Szczepański
BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values...
March 9, 2018: Journal of Immunological Methods
Dmitrijs Rots, Madara Kreile, Sergejs Nikulshin, Zhanna Kovalova, Linda Gailite
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study...
March 12, 2018: Pediatric Hematology and Oncology
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease...
March 12, 2018: Expert Opinion on Therapeutic Targets
Jeannine S McCune
Immunotherapy is now the fourth pillar of cancer therapy, with surgery, radiation, and traditional chemotherapy being the remaining pillars. Over the past decade, enthusiasm for immunotherapy has increased because of, in part, data showing that it consistently improves overall survival in select patients with historically refractory cancers. This issue covers various aspects of immunotherapy ranging from use of 1) chimeric antigen receptor (CAR) T cells to treat patients with B-cell acute lymphoblastic leukemia; 2) population pharmacokinetic/dynamic modeling to develop new immune checkpoint inhibitors; and 3) simulations of existing population pharmacokinetic models of immunotherapy to minimize waste without compromising exposure and efficacy...
April 2018: Clinical Pharmacology and Therapeutics
P Dallé Rosa, M Ramirez-Castrillon, P Valente, A Meneghello Fuentefria, A D Van Diepeningen, L Z Goldani
Invasive fusariosis has a high mortality and is predominantly observed in patients with leukemia. We report the first case of a novel species of Fusarium, Fusarium riograndense sp. nov, isolated from a lesion in the nasal cavity lesion of a patient with acute lymphoblastic leukemia. The etiological agent was identified by Multilocus Sequencing Typing (MLST), including RPB2, TEF-1α, and ITS-LSU sequences, the gold standard technique to identify new species of Fusarium. MLST and phenotypic data strongly supported its inclusion in the F...
March 7, 2018: Journal de Mycologie Médicale
Meghdad Abdollahpour-Alitappeh, Seyed Masoud Hashemi Karouei, Majid Lotfinia, Amir Amanzadeh, Mahdi Habibi-Anbouhi
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE)...
March 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Wei Liu, Yin Ting Cheung, Tara M Brinkman, Pia Banerjee, Deokumar Srivastava, Vikki G Nolan, Hongmei Zhang, James G Gurney, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Kevin R Krull
BACKGROUND: Prevalence of emotional, behavioral and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia (ALL) treated on a chemotherapy-only protocol were not well defined. METHODS: Self- and parent-reported emotional and behavioral symptoms were assessed for 161 survivors of childhood ALL (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post-diagnosis). Age- and sex-adjusted scores were calculated for standardized measures, and compared to 90th percentile of norms...
March 9, 2018: Psycho-oncology
Rene Marke, Frank N van Leeuwen, Blanca Scheijen
Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 gene defects are associated with inferior treatment outcome in both childhood and adult BCP-ALL and occur in more than 70% of BCR-ABL1 positive and BCR-ABL1-like ALL cases. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome...
March 8, 2018: Haematologica
Luca Trentin, Manon Queudeville, Sarah Mirjam Eckhoff, Md Nabiul Hasan, Vera Münch, Elena Boldrin, Felix Seyfried, Stefanie Enzenmüller, Klaus-Michael Debatin, Lüder Hinrich Meyer
In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations as defined by surface markers have shown equal abilities to reconstitute leukemia upon transplantation onto immunodeficient mice. Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, we have functionally characterized leukemia-initiating cells and found that cells in all cell cycle stages are able to reconstitute leukemia in vivo, with early cycling cells (G1blow population) exhibiting the highest leukemia-initiating potential...
March 8, 2018: Haematologica
Nadine Farah, Amy A Kirkwood, Sunniyat Rahman, Theresa Leon, Sarah Jenkinson, Rosemary E Gale, Katharine Patrick, Jeremy Hancock, Sujith Samarasinghe, David C Linch, Anthony V Moorman, Nicholas Goulden, Ajay Vora, Marc R Mansour
No abstract text is available yet for this article.
March 8, 2018: Haematologica
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