Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia?

Rieger, Christina T. und Fiegl, Michael (2016): Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia? In: Experimental Hematology, Bd. 44, Nr. 7: S. 578-582

Abstract

Reduced oxygen partial pressure (pO(2)) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1 alpha) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO(2). However, in contrast to solid tumors, in this context, the low pO(2) is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO(2) as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO(2). Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO(2): they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO(2) should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms;therefore, a strict distinction should be made between physiologically low pO(2) (physoxia) and hypoxia. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by ELSEVIER.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0301-472X
• Sprache: Englisch