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The interleukin-3 receptor CD123 targeted SL-401 mediates potent cytotoxic activity against CD34+CD123+ cells from acute myeloid leukemia/myelodysplastic syndrome patients and healthy donors.
Mani, Rajeswaran; Goswami, Swagata; Gopalakrishnan, Bhavani; Ramaswamy, Rahul; Wasmuth, Ronni; Tran, Minh; Mo, Xiaokui; Gordon, Amber; Bucci, Donna; Lucas, David M; Mims, Alice; Brooks, Christopher; Dorrance, Adrienne; Walker, Alison; Blum, William; Byrd, John C; Lozanski, Gerard; Vasu, Sumithira; Muthusamy, Natarajan.
Afiliación
  • Mani R; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Goswami S; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Gopalakrishnan B; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Ramaswamy R; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Wasmuth R; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Tran M; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Mo X; Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
  • Gordon A; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Bucci D; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Lucas DM; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Mims A; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Brooks C; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Dorrance A; Stemline Therapeutics, Inc., New York, NY, USA.
  • Walker A; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Blum W; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Byrd JC; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Lozanski G; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Vasu S; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Muthusamy N; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
Haematologica ; 103(8): 1288-1297, 2018 08.
Article en En | MEDLINE | ID: mdl-29773600
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia. Here, we report indiscriminate killing of CD123+ normal and acute myeloid leukemia / myelodysplastic syndrome cells by SL-401, a diphtheria toxin interleukin-3 fusion protein. SL-401 induced cytotoxicity of CD123+ primary cells/blasts from acute myeloid leukemia and myelodysplastic syndrome patients but not CD123- lymphoid cells. Importantly, SL-401 was highly active even in cells expressing low levels of CD123, with minimal effect on modulation of the CD123 target in acute myeloid leukemia. SL-401 significantly prolonged survival of leukemic mice in acute myeloid leukemia patient-derived xenograft mouse models. In addition to primary samples, studies on normal cord blood and healthy marrow show that SL-401 has activity against normal hematopoietic progenitors. These findings indicate potential use of SL-401 as a "bridge-to-transplant" before allogeneic hematopoietic cell transplantation in acute myeloid leukemia / myelodysplastic syndrome patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Proteínas Recombinantes de Fusión / Leucemia Mieloide Aguda / Linfocitos T CD4-Positivos / Subunidad alfa del Receptor de Interleucina-3 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Italia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Proteínas Recombinantes de Fusión / Leucemia Mieloide Aguda / Linfocitos T CD4-Positivos / Subunidad alfa del Receptor de Interleucina-3 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Italia