Update on acute myeloid leukemia stem cells: New discoveries and therapeutic opportunities.
The existence of cancer stem cells has been well established in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells (LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells (HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitorsin vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the self-renewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.
Maximilian Stahl, Tae Kon Kim, Amer M Zeidan, Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510-3222, United States.
Maximilian
M
Stahl
Maximilian Stahl, Tae Kon Kim, Amer M Zeidan, Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510-3222, United States.
Tae Kon
TK
Kim
Maximilian Stahl, Tae Kon Kim, Amer M Zeidan, Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510-3222, United States.
Amer M
AM
Zeidan
Acute myeloid leukemia; C-X-C chemokine receptor type 4; Cancer stem cells; Leukemia stem cells; NF-κB; Plerixafor; Stem cell niche; Xenotransplantation