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Mesenchymal stromal cells confer chemoresistance to myeloid leukemia blasts through Side Population functionality and ABC transporter activation.
Boutin, Laetitia; Arnautou, Pierre; Trignol, Aurélie; Ségot, Amandine; Farge, Thomas; Desterke, Christophe; Soave, Sabrina; Clay, Denis; Raffoux, Emmanuel; Sarry, Jean-Emmanuel; Malfuson, Jean-Valère; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Anginot, Adrienne.
Afiliação
  • Boutin L; CTSA, IRBA, Clamart.
  • Arnautou P; Inserm UMR-S-MD1197, Paul Brousse Hospital, Paris 11 University, Villejuif.
  • Trignol A; Hematology Department, HIA Percy, Clamart.
  • Ségot A; CTSA, IRBA, Clamart.
  • Farge T; Hematology Department, HIA Percy, Clamart.
  • Desterke C; Inserm U1037, Cancer Research Center of Toulouse, University of Toulouse, Toulouse.
  • Soave S; Inserm UMS33, Paul Brousse Hospital, Paris 11 University, Villejuif.
  • Clay D; Inserm UMR-S-MD1197, Paul Brousse Hospital, Paris 11 University, Villejuif.
  • Raffoux E; Inserm UMS33, Paul Brousse Hospital, Paris 11 University, Villejuif.
  • Sarry JE; Adult Hematology Department, Saint Louis Hospital, Paris, France.
  • Malfuson JV; Inserm U1037, Cancer Research Center of Toulouse, University of Toulouse, Toulouse.
  • Lataillade JJ; Inserm UMR-S-MD1197, Paul Brousse Hospital, Paris 11 University, Villejuif.
  • Le Bousse-Kerdilès MC; Hematology Department, HIA Percy, Clamart.
  • Anginot A; CTSA, IRBA, Clamart.
Haematologica ; 105(4): 987-9998, 2020 04.
Article em En | MEDLINE | ID: mdl-31289201
Targeting chemoresistant malignant cells is one of the current major challenges in oncology. Therefore, it is mandatory to refine the characteristics of these cells to monitor their survival and develop adapted therapies. This is of particular interest in acute myeloid leukemia (AML), for which the 5-year survival rate only reaches 30%, regardless of the prognosis. The role of the microenvironment is increasingly reported to be a key regulator for blast survival. In this context, we demonstrate that contact with mesenchymal stromal cells promotes a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation leads to the induction of a Side Population (SP) phenotype in a subpopulation of primary leukemia blasts through alpha (α)4 engagement. The stroma-promoting effect is reversible and is observed with stromal cells isolated from either healthy donors or leukemia patients. Blasts expressing an SP phenotype are mostly quiescent and are chemoresistant in vitro and in vivo in patient-derived xenograft mouse models. At the transcriptomic level, blasts from the SP are specifically enriched in the drug metabolism program. This detoxification signature engaged in contact with mesenchymal stromal cells represents promising ways to target stroma-induced chemoresistance of AML cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Leucemia / Tratamento Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Haematologica Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Leucemia / Tratamento Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Haematologica Ano de publicação: 2020 Tipo de documento: Article