The increase in levels of the hormone erythropoietin, which leads to increased production of red blood cells in response to hypoxia, was a physiological response known in the early 20th century. However, the mechanism of the cellular reaction to hypoxia was unknown. William G. Kaelin Jr., Peter J. Ratcliffe, and Gregg L. Semenza received the 2019 Nobel Prize in Physiology and Medicine for their contributions to this field. HIFs have been identified as transcription factors that function in response to hypoxia. When oxygen levels are low, the HIF protein complex is protected from degradation and accumulates in the nucleus, where it connects with the aryl hydrocarbon receptor nuclear translocator (ARNT/HIF1-β) and binds to specific DNA sequences (HREs) in hypoxia-regulated genes. At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome. Oxygen regulates the degradation process by adding hydroxyl groups (OH) to HIF-1α. The VHL protein can then recognize HIF and form a complex that leads to its degradation in an oxygen-dependent manner (1,2). It is known that there are 3 types of HIF: HIF-1, HIF-2, and HIF-3. Hypoxia activates all three HIFs, with HIF-3 acting as a regulator by suppressing the gene expression of HIF-1 and HIF-2. All three HIFs consist of two subunits, α and β. The β subunit is consistently expressed in the nucleus, independent of oxygen levels, whereas the α subunit exhibits differential responses to hypoxia and normoxia, serving as the primary site for HIF-1 in tumorigenesis. To date, three isoforms of the HIF α-subunit have been identified; these are HIF-1α, -2α, and -3α. In particular, HIF-1α is the most extensively studied isoform and is generally expressed in human cells. HIF-2α is expressed only in specific tissues and cell types, such as the lung, kidney, and liver. HIF-3α is mainly expressed in heart, kidney, and lung epithelial cells. Two genes, ARNT1 and ARNT2, encode HIF-1β subunits. HIF1A, EPAS1, and HIF3A encode the HIF1/2/3α proteins, respectively. HIF-1a has been detected in high amounts in many types of cancer and is known to regulate the expression of over 100 genes.It has an effect on gene categories related to angiogenesis, energy metabolism, invasion and metastasis, proliferation and apoptosis-related proteins, immune evasion, and drug resistance, which are important steps in tumor homeostasis (3).This makes the HIF pathway a targetable focus in cancer treatment. Studies have shown that there is an increase in HIF-1α and HIF-2α expression in AML and that suppression of HIF-1α induces apoptosis (4-5). It has also been shown that hypoxic environment and HIF pathway play an important role in the long-term survival of leukemic stem cells in the bone marrow. However, there are also studies showing that HIF-1α deficiency causes AML to progress more rapidly (6).Therefore, these findings indicate that the role of HIF-1α should be considered carefully in practical applications depending on specific conditions. Pre- and post-clinical studies targeting the HIF pathway are ongoing. The HIF pathway appears promising as a new therapeutic target.