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ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype.
Lucena-Araujo, Antonio R; Coelho-Silva, Juan L; Pereira-Martins, Diego A; Thomé, Carolina; Scheucher, Priscila S; Lange, Ana P; Paiva, Helder H; Hemmelgarn, Benjamin T; Morais-Sobral, Mariana C; Azevedo, Elisa A; Franca-Neto, Pedro L; Franca, Rafael F; Silva, Cleide L; Krause, Alexandre; Rego, Eduardo M.
Afiliación
  • Lucena-Araujo AR; Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.
  • Coelho-Silva JL; Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
  • Pereira-Martins DA; Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
  • Thomé C; Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
  • Scheucher PS; Center for Cell Based Therapy, University of Sao Paulo, Ribeirao Preto, Brazil.
  • Lange AP; Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.
  • Paiva HH; Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.
  • Hemmelgarn BT; Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.
  • Morais-Sobral MC; The Ohio State University, Columbus, USA.
  • Azevedo EA; Department of Microbiology, Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil.
  • Franca-Neto PL; Department of Virology, Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil.
  • Franca RF; Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
  • Silva CL; Department of Virology, Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil.
  • Krause A; Center for Cell Based Therapy, University of Sao Paulo, Ribeirao Preto, Brazil.
  • Rego EM; Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.
Oncotarget ; 8(5): 8475-8483, 2017 Jan 31.
Article en En | MEDLINE | ID: mdl-28035072
Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis. Next, we evaluated the effect of ΔNp73 on stem-cell self-renewal and myeloid differentiation. Primary BM cells lentivirally infected with human ΔNp73 were not immortalized in culture and did not present significant changes in the percentage of CD11b. Finally, we assessed the impact of ΔNp73 on leukemogenesis or its possible cooperation with PML/RARA fusion protein in the induction of an APL-leukemic phenotype. After 120 days of follow-up, all transplanted mice were clinically healthy and, no evidence of leukemia/myelodysplasia was apparent. Taken together, our data suggest that ΔNp73 had no leukemic transformation capacity by itself and apparently did not cooperate with the PML/RARA fusion protein to induce a leukemic phenotype in a murine BM transplantation model. In addition, the forced expression of ΔNp73 in murine BM progenitors did not alter the ATRA-induced differentiation rate in vitro or induce aberrant cell proliferation, but exerted an important role in cell survival, providing resistance to drug-induced apoptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia / Apoptosis / Proteína Tumoral p73 / Proteína de la Leucemia Promielocítica / Receptor alfa de Ácido Retinoico Tipo de estudio: Prognostic_studies Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia / Apoptosis / Proteína Tumoral p73 / Proteína de la Leucemia Promielocítica / Receptor alfa de Ácido Retinoico Tipo de estudio: Prognostic_studies Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos