Details

Autor(en) / Beteiligte

• Zeng, Andy G X
• Bansal, Suraj
• Jin, Liqing
• Mitchell, Amanda
• Chen, Weihsu Claire
• Abbas, Hussein A
• Chan-Seng-Yue, Michelle
• Voisin, Veronique
• van Galen, Peter
• Tierens, Anne
• Cheok, Meyling
• Preudhomme, Claude
• Dombret, Hervé
• Daver, Naval
• Futreal, P Andrew
• Minden, Mark D
• Kennedy, James A
• Wang, Jean C Y
• Dick, John E

Titel

A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia

Ist Teil von

• Nature Medicine, 2022-06, Vol.28 (6), p.1212-1223

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor and mature cell types. Leukemia hierarchy composition was associated with functional, genomic and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP and Intermediate. Critically, variation in hierarchy composition along the Primitive versus GMP or Primitive versus Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A seven-gene biomarker derived from the Primitive versus Mature axis was associated with response to 105 investigational drugs. Cellular hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.