Table 1.
The functional roles of HIF-1α in diverse types of hematological malignancies.
| Cancer type | Patients or cell lines | Role of HIF-1α in cancer | Functions | Molecular mechanisms | Reference |
|---|---|---|---|---|---|
| ALL | ALL cells/mice | Oncogene | Deferoxamine (DFO) inhibited the proliferation and growth of tumor cells and induced apoptosis in ALL cells by inactivating ROS/HIF-1α signaling. | DFO/ROS/HIF-1α | 92 |
| BM samples of ALL patients/leukemia cell lines | Oncogene | Chemical inhibition of HIF-1α induced down-regulation of YY1, sensitizing cells to chemotherapeutic agents. | HIF-1α/YY1 | 93 | |
| Human T-ALL cell samples/mice | Oncogene | HIF-1α KD restored the activity of mTOR at low oxygen concentrations, thereby regaining chemosensitivity in T-ALL cells. | HIF-1α/mTOR | 94 | |
| CLL | lines/mice | Oncogene | SC could induce up-regulation of HIF-1α in CLL cells, ultimately promoting the survival of CLL cells. | HIF-α/CXCL12/CXCR4 | 95 |
| PB samples of CLL/cell lines/mice | Oncogene | In the TP53-disrupted (TP53dis) subset, the accumulation of HIF-1α led to reduced apoptosis and drug resistance in CLL cells when hypoxic. | pVHL/HIF-1α | 96 | |
| CLL patients/a murine model | Oncogene | The relevant drugs inhibited the growth of CLL cells by suppressing HIF-1α and interfering with intracellular redox homeostasis. | HIF-1α/oxidative stress | 97 | |
| Primary CLL cells/CLL cell lines/mice | Oncogene | EZN-2208, confirmed to inhibit HIF-1α, could increase the response to fludarabine by promoting apoptosis in CLL cells. | EZN-2208/HIF-1α | 98 | |
| AML | AML patients/AML cells/mice | Oncogene | PARP14 induced the growth of AML cells and glycolysis via activating NF-κB and facilitating the expression of HIF-1α. | PARP14/NF-κB/HIF-1α | 99 |
| Cell lines | Oncogene | Simvastatin inhibited the proliferation, migration, and invasion, and promoted apoptosis of AML cells by modulating the miR-19a-3p/HIF-1α axis. | Simvastatin/miR-19a-3p/HIF-1α | 45 | |
| THP-1 and HL-60 cells | Oncogene | Under hypoxia, CXCL2 promoted the proliferation and migration of AML cells by enhancing the activity of HIF-1α and up-regulating PIM2 expression. | CXCL2/HIF-1α/PIM2, mTOR | 100 | |
| AML cells | Oncogene | Inhibition of HIF-1α could down-regulate the expression of YAP in AML cells, thereby re-sensitizing AML cells to ADR in hypoxia. | HIF-1α/YAP | 101 | |
| AML patients/AML cell lines/mice | Oncogene | Echinomycin could effectively treat patients with TP53-mutated AML via inhibiting HIF-1α. | Echinomycin/HIF-1α | 102 | |
| Healthy donor mesenchymal stromal cells/patient samples/AML cell lines | Oncogene | Abrogation of STC1 (stanniocalcin 1) or HIF-1α attenuated the inhibition of HSPC differentiation and proliferation by AML. | HIF-1α/STC1 | 103 | |
| CML | TKIs sensitive and resistant CML cells | Oncogene | HIF-1α could facilitate the expression of BCR-ABL1 and Met to rescue CML cells from death. | HIF-1α/BCR-ABL1, Met | 104 |
| K-562 cells | Oncogene | 2-methoxyestradiol (2-ME2) induced apoptosis in CML cells by suppressing the expression of HIF-1α and down-regulating C-Myc or Bcl-xl and Bcl-2 genes. | 2-ME2/HIF-1α/C-Myc, Bcl-xl or Bcl-2 | 105 | |
| CML patients/CML cell lines/mice | Oncogene | Tri-CAP (trident cold atmospheric plasma) could disrupt cancer survival pathways such as proliferative AKT/mTOR/HIF-1α signaling, thereby inducing apoptosis of tumor cells. | Tri-CAP/AKT/mTOR/HIF-1α | 106 | |
| lymphoma | T-cell lymphoma cells | Oncogene | Sildenafil suppressed the expression of HIF-1α and decreased glucose metabolism, thus enhancing the killing ability of cisplatin on tumor cells. | HIF-1α/glycolysis regulatory molecules/ROS | 107 |
| Mice | Oncogene | In in vivo experiments, MJ promoted T-cell lymphoma cell death by docking with prominent binding sites for HIF-1α, HK2, and Hsp70. | MJ/HIF-1α | 108 | |
| Tumor cell line Hut78/mice | Oncogene | Inhibition of HIF-1α blocked the glycolysis and IL-17 pathways induced by CHOP chemotherapy. | HIF-1α/glycolysis/IL-17 | 109 | |
| MM | MM cell lines | Oncogene | Macitentan down-regulated HIF-1α and the transcription and release of downstream pro-angiogenic cytokines, curbing the growth of MM cells. | ET-1/HIF-1α/pro-angiogenic cytokines | 110 |
| MM patients/mice | Oncogene | Low expression of miR-411-3p could promote malignant proliferation and tumor stem cell-like properties of MM by activating HIF-1α. | lncRNA ANRIL/miR-411-3p/HIF-1α | 111 |
Abbreviations: DFO: Deferoxamine; mTOR: rapamycin; SC: stromal cell; BM: bone marrow; PB: peripheral blood; pVHL: von Hippel-Lindau tumor suppressor protein; YAP: yes-associated protein; ADR: adriamycin; 2-ME2: 2-Methoxyestradiol; MSCs: mesenchymal stromal cells; STC1: stanniocalcin 1; Tri-CAP: trident cold atmospheric plasma; PIM2: proviral integration moloney 2; ROS: reactive oxygen species; HK2: hexokinase 2; MJ: methyl jasmonate.