Tags

Type your tag names separated by a space and hit enter

NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia.
Sci Rep. 2020 Jun 25; 10(1):10315.SR

Abstract

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.

Authors+Show Affiliations

Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Department of Clinical Analyses, Toxicology and Food Sciences, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil.Department of Clinical Analyses, Toxicology and Food Sciences, University of São Paulo, Ribeirão Preto, Brazil.Hematology, Medical School, University of São Paulo, São Paulo, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Department of Internal Medicine, University of Pernambuco, Recife, Brazil.Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil.Hematology Division, Federal University of Paraná, Curitiba, Brazil.Hematology Division, Federal University of Paraná, Curitiba, Brazil.Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil.Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil.Federal University of São Paulo, São Paulo, Brazil.Federal University of São Paulo, São Paulo, Brazil.Cell Therapy Program, Princess Margaret Cancer Centre, Toronto, Canada.Leukemia Service, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York, USA.Department of Oncology, St. Jude Children's Research Hospital, Memphis, USA.Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands.Santa Lucia Foundation, Rome, Italy.Department of Biopathology, Tor Vergata University, Rome, Italy. Santa Lucia Foundation, Rome, Italy.Department of Hematology, Valencia University Medical School, Valencia, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.Regional Blood Center of Ribeirão Preto, Medical School of Ribeirão Preto, Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil. eduardo.rego@fm.usp.br. LIM31, Hematology, Medical School, University of São Paulo, São Paulo, Brazil. eduardo.rego@fm.usp.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32587277

Citation

Thomé, Carolina Hassibe, et al. "NTAL Is Associated With Treatment Outcome, Cell Proliferation and Differentiation in Acute Promyelocytic Leukemia." Scientific Reports, vol. 10, no. 1, 2020, p. 10315.
Thomé CH, Ferreira GA, Pereira-Martins DA, et al. NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. Sci Rep. 2020;10(1):10315.
Thomé, C. H., Ferreira, G. A., Pereira-Martins, D. A., Dos Santos, G. A., Ortiz, C. A., de Souza, L. E. B., Sobral, L. M., Silva, C. L. A., Scheucher, P. S., Gil, C. D., Leopoldino, A. M., Silveira, D. R. A., Coelho-Silva, J. L., Traina, F., Koury, L. C., Melo, R. A. M., Bittencourt, R., Pagnano, K., Pasquini, R., ... Rego, E. M. (2020). NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. Scientific Reports, 10(1), 10315. https://doi.org/10.1038/s41598-020-66223-2
Thomé CH, et al. NTAL Is Associated With Treatment Outcome, Cell Proliferation and Differentiation in Acute Promyelocytic Leukemia. Sci Rep. 2020 Jun 25;10(1):10315. PubMed PMID: 32587277.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. AU - Thomé,Carolina Hassibe, AU - Ferreira,Germano Aguiar, AU - Pereira-Martins,Diego Antonio, AU - Dos Santos,Guilherme Augusto, AU - Ortiz,César Alexander, AU - de Souza,Lucas Eduardo Botelho, AU - Sobral,Lays Martins, AU - Silva,Cleide Lúcia Araújo, AU - Scheucher,Priscila Santos, AU - Gil,Cristiane Damas, AU - Leopoldino,Andréia Machado, AU - Silveira,Douglas R A, AU - Coelho-Silva,Juan L, AU - Traina,Fabíola, AU - Koury,Luisa C, AU - Melo,Raul A M, AU - Bittencourt,Rosane, AU - Pagnano,Katia, AU - Pasquini,Ricardo, AU - Nunes,Elenaide C, AU - Fagundes,Evandro M, AU - Gloria,Ana Beatriz F, AU - Kerbauy,Fábio Rodrigues, AU - Chauffaille,Maria de Lourdes, AU - Keating,Armand, AU - Tallman,Martin S, AU - Ribeiro,Raul C, AU - Dillon,Richard, AU - Ganser,Arnold, AU - Löwenberg,Bob, AU - Valk,Peter, AU - Lo-Coco,Francesco, AU - Sanz,Miguel A, AU - Berliner,Nancy, AU - Faça,Vitor Marcel, AU - Rego,Eduardo M, Y1 - 2020/06/25/ PY - 2020/01/07/received PY - 2020/05/15/accepted PY - 2020/6/27/entrez PY - 2020/6/27/pubmed PY - 2020/6/27/medline SP - 10315 EP - 10315 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32587277/NTAL_is_associated_with_treatment_outcome,_cell_proliferation_and_differentiation_in_acute_promyelocytic_leukemia L2 - http://dx.doi.org/10.1038/s41598-020-66223-2 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.