Técnicas Avançadas em Biologia e Medicina
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Iron Metabolism and Leukemia

Wen-Chi Yang

Iron is an important regulator of cell growth, apoptosis and enzymatic functions. Many cancers, including soft tissue sarcoma, mesothelioma, renal cell carcinoma, colorectal cancer, gastric cancer, lung cancer, hepatocellular carcinoma, and endometriosis have been associated with iron overload. Iron metabolism is also affected in leukemia, and iron chelators can inhibit proliferation of leukemia cells. Lipocalin 2 (LCN2) is an iron transporter that plays important roles in cellular metabolism, growth and differentiation, and host immune response. Siderophores are small iron-binding molecules that facilitate microbial and mammalian cells iron transport. Type 2 Hydroxy Butyrate Dehydrogenase (BDH2), a member of the short-chain dehydrogenase family, is a rate-limiting factor in the biogenesis of the mammalian siderophores. In our previous studies, we reported that LCN2 is a good prognostic marker in patients with Cytogenetically Normal Acute Myeloid Leukemia (CN-AML), and BDH2 predicts poor prognosis in CN-AML patients. Expression levels of both LCN2 and BDH2 genes are independent from other well-known gene alterations and clinical characteristics of CN-AML patients. They may - (pass through does not make sense) induce or inhibit apoptosis during Reactive Oxygen Species (ROS) challenges. We have also demonstrated that higher BDH2 expressions are associated with a greater chance of leukemic transformation in Myelodysplasia Syndrome (MDS) patients. Since the level of BDH2 expression directly correlates with the serum ferritin concentration in MDS patients, iron metabolism may have important roles in tumor transformation. In this review, we summarize evidence of how iron metabolism and iron transporters influence the prognosis of leukemia.