Targeting hypoxia in the leukemia microenvironment.
The bone marrow (BM) microenvironment regulates survival and maintenance of normal hematopoietic stem cells. Within the endosteal niche, hypoxia has an essential role in maintenance of the primitive quiescent hematopoietic stem cell. We and others have demonstrated that in the context of hematologic malignancies the BM is highly hypoxic, and that progression of the disease is associated with expansion of hypoxic niches and stabilization of the oncogenic HIF-1α. This review will provide an overview of the normal and leukemic BM microenvironment with a special emphasis on pathological hypoxia including the development of hypoxia-activated prodrugs and their applicability in hematological malignancies.
Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030, USA.
Juliana
J
Benito
Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030, USA.
Zhihong
Z
Zeng
Division of Cancer Medicine - Unit 448, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030, USA.
Marina
M
Konopleva
Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland, New Zealand.
William R
WR
Wilson