The Heme Oxygenase System in Hematological Malignancies

SIGNIFICANCE: Several lines of evidence suggest that hematological malignancies exhibit an altered redox balance homeostasis that can lead to the activation of various survival pathways that, in turn, lead to the progression of disease and chemoresistance. Among these pathways, the heme oxygenase-1 (HO-1) pathway is likely to play a major role. HO catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. This review focuses on the role of HO-1 in various hematological malignancies and the possibility of exploiting such targets to improve the outcome of well-established chemotherapeutic regimens. Recent Advances and Critical Issues: Interestingly, the inhibition of the expression of HO-1 (e.g., with siRNA) or HO activity (with competitive inhibitors) contributes to the increased efficacy of chemotherapy and improves the outcome in animal models. Furthermore, some hematological malignancies (e.g., chronic myeloid leukemia and multiple myeloma) have served to explore the non-canonical functions of HO-1, such as the association between nuclear compartmentalization and genetic instability and/or chemoresistance. FUTURE DIRECTIONS: The HO system may serve as an important tool in the field of hematological malignancies because it can be exploited to counteract chemoresistance and to monitor the outcome of bone marrow transplants and may be an additional target for combined therapies. Antioxid. Redox Signal. 27, 363-377.