Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?
Blood Rev
; 65: 101184, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38493006
ABSTRACT
E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 trial of MEC chemotherapy combined with uproleselan for relapsed/refractory AML showed a median overall survival of 8.8 months and low (2%) rates of severe oral mucositis. Clinical trials seek to confirm activity in AML and mitigation of neutrophil-mediated adverse events (mucositis and diarrhea) after intensive chemotherapy. In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Neoplasias Hematológicas
Límite:
Humans
Idioma:
En
Revista:
Blood Rev
Asunto de la revista:
HEMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos