Moving Myeloid Leukemia Drug Discovery Into the Third Dimension

Frontiers in Pediatrics

article

Donna M. Cartledge Wolf¹  Sigrid A. Langhans¹ 

[1] Nemours Center for Childhood Cancer Research, Nemours/Alfred I. duPont Hospital for Children, United States

关键词: three-dimensional cell culture;    bone marrow;    leukemia;    AML;    tumor microenvironment;   

DOI  :  10.3389/fped.2019.00314

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

The development of therapies aimed at leukemia has progressed substantially in the past years but childhood acute myeloid leukemia (AML) remains one of the most challenging cancers to treat. Genomic profiling of AML has greatly enhanced our understanding of the genetic and epigenetic landscape of this high-risk leukemia. With it comes the opportunity to develop targeted therapies that are expected to be more effective and less toxic than current treatment regimens. Nevertheless, often overlooked in leukemia drug discovery are the dynamic interactions between leukemic cells and the bone marrow environment. The interplay between leukemic cells, stromal cells and the extracellular matrix plays critical roles in the development, progression and relapse of AML as well as in drug response and the development of resistance. Here we will review pediatric leukemia with a special focus on acute myeloid disease in children, and discuss the tumor microenvironment in the context of drug resistance and leukemia stem cell survival. We will emphasize how three-dimensional (3D) cell-based drug discovery may offer hope for both the identification and advancement of more effective treatment options for patients suffering from this devastating disease.

【 授权许可】

CC BY