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Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy.
Ngo, Steven; Oxley, Ethan P; Ghisi, Margherita; Garwood, Maximilian M; McKenzie, Mark D; Mitchell, Helen L; Kanellakis, Peter; Susanto, Olivia; Hickey, Michael J; Perkins, Andrew C; Kile, Benjamin T; Dickins, Ross A.
Afiliación
  • Ngo S; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Oxley EP; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Ghisi M; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Garwood MM; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • McKenzie MD; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.
  • Mitchell HL; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Kanellakis P; Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Susanto O; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC, 3168, Australia.
  • Hickey MJ; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC, 3168, Australia.
  • Perkins AC; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.
  • Kile BT; Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Dickins RA; Australian Centre for Blood Diseases, Monash University, 99 Commercial Rd, Melbourne, VIC, 3004, Australia. ross.dickins@monash.edu.
Nat Commun ; 12(1): 6546, 2021 11 11.
Article en En | MEDLINE | ID: mdl-34764270
Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapy-induced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy-induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy-resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Neoplasia Residual Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Neoplasia Residual Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido