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CD37 in acute myeloid leukemia: a novel surface target for drug delivery.
Jeremy, Erin; Artiga, Esthela; Elgamal, Sara; Cheney, Carolyn M; Eicher, Dalen; Zalponik, Kevan; Orwick, Shelley; Mao, Hsiao-Yin Charlene Charlene; Wasmuth, Ronni; Harrington, Bonnie K; Mustonen, Allison; Beshay, Peter; Halley, Patrick; Castro, Carlos; Williams, Katie E; Hing, Zachary A; Chen, Timothy L; Lucas, Christopher R; Vantangoli, Nicholas J; Lapalombella, Rosa; Grieselhuber, Nicole Renee; Mo, Xiaokui M; Hertlein, Erin; Muthusamy, Natarajan; Mundy-Bosse, Bethany L; Byrd, John C; Larkin, Karilyn.
Afiliación
  • Jeremy E; The Ohio State University Wexner Medical Center, Columbus, Ohio, United States.
  • Artiga E; The Ohio State University, Columbus, Ohio, United States.
  • Elgamal S; The Ohio State University, Columbus, Ohio, United States.
  • Cheney CM; University of Cincinnati, United States.
  • Eicher D; The Ohio State University, Columbus, Ohio, United States.
  • Zalponik K; The Ohio State University, Columbus, Ohio, United States.
  • Orwick S; The Ohio State University, Columbus, Ohio, United States.
  • Mao HCC; Ohio State University, Columbus, Ohio, United States.
  • Wasmuth R; Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States.
  • Harrington BK; Michigan State University, United States.
  • Mustonen A; The Ohio State University, Columbus, Ohio, United States.
  • Beshay P; The Ohio State University, Columbus, Ohio, United States.
  • Halley P; The Ohio State University, Columbus, Ohio, United States.
  • Castro C; The Ohio State University, Columbus, Ohio, United States.
  • Williams KE; The Ohio State University, columbus, Ohio, United States.
  • Hing ZA; University of Pennsylvania, United States.
  • Chen TL; The Ohio State University, Columbus, Ohio, United States.
  • Lucas CR; The Ohio State University, Columbus, Ohio, United States.
  • Vantangoli NJ; The Ohio State University, Columbus, Ohio, United States.
  • Lapalombella R; The Ohio State University, columbus, Ohio, United States.
  • Grieselhuber NR; The Wexner Medical Center at Ohio State University, Columbus, Ohio, United States.
  • Mo XM; Ohio State University, columbus, Ohio, United States.
  • Hertlein E; University of Cincinnati, Cincinnati, Ohio, United States.
  • Muthusamy N; The Ohio State University, Columbus, Ohio, United States.
  • Mundy-Bosse BL; The Ohio State University, Columbus, Ohio, United States.
  • Byrd JC; The University of Cincinnati, Cincinnati, Ohio, United States.
  • Larkin K; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States.
Blood Adv ; 2024 Sep 30.
Article en En | MEDLINE | ID: mdl-39348689
ABSTRACT
Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes which limits broad applicability of targeted therapy. We discovered that the hematopoietic restricted tetraspanin CD37 is expressed on all primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype. We demonstrate that the internalization properties of CD37 are distinct in AML blasts when compared to normal blood cells, and that CD37 rapidly accumulates inside AML blasts via dynamin-dependent endocytosis. Our work revealed that the clinically relevant anti-CD37 antibody drug conjugate (ADC) Debio 1562 (αCD37-DM1) is highly cytotoxic to AML blasts, but not normal hematopoietic stem cells. We found that αCD37-DM1 improved clinical outcomes and overall survival in multiple in vivo models of AML. Together, these data demonstrate that targeting CD37 with an ADC such as αCD37-DM1 is a feasible and promising therapeutic option for the treatment of AML.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos