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Leukemia also spelled leukaemia, is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. Leukemia is a group of blood cancers that usually result in high numbers of abnormal blood cells. Many types exist such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML).
Fig.1 Immunotherapy targets for acute myeloid leukemia and acute lymphoblastic leukemia
Targeted therapies are expected to be more effective and less toxic than current treatment regimens，such as chemotherapy, radiation therapy and bone marrow transplant. The advent of small molecule-based targeted therapy has improved the treatment of both acute and chronic leukemias. Targeted therapy drugs which are generally available for leukemia are listed below.
| Target | Types | Agent | Manufacturer | Start Marketing Date |
|---|---|---|---|---|
| CD19, CD3 | DAB | Blincyto | Amgen | 2014 |
| BCR, ABL1 | Small molecule | Bosulif | Pfizer | 2012 |
| Bcr-Abl | Small molecule | Sprycel | BMS | 2006 |
| BTK | Small molecule | Imbruvica | J&J/Abbvie | 2013 |
| PIK3CA | Small molecule | Zydelig | Gilead | 2014 |
| Bcr-Abl | Small molecule | Gleevec | Novartis | 2000 |
| Bcr-Abl, PDGFRB, KIT | Small molecule | Tasigna | Novartis | 2007 |
| CD20(MS4A1) | Small molecule | Gazyva | Roche | 2013 |
| CD20(MS4A1) | mAb | Arzerra | GSK | 2009 |
| Bcr-Abl | Small molecule | Iclusig | Ariad | 2012 |
| CD20(MS4A1) | mAb | Rituxan | Roche | 1997 |
| BCL-2 | Small molecule | Venclexta | Abbive | 2016 |
| Ab | Ultomiris | Servier pharma | 2018 | |
| Ab | Ultomiris | Alexion pharmaceutical | 2018 | |
| IDH2 | Small molecule | Idhifa | Celgene | 2017 |
| CD123 | Ab | Elzonris | Stemline Therautics | 2018 |
| IDH1 | Small molecule | Tibsovo | Agios pharmaceuticals | 2018 |
| CD33 | Ab | Mylotarg | Pfizer | 2017 |
| FLT3 | Small molecule | Rydapt | Novartis | 2017 |
| CD22 | Ab | Besponsa | Pfizer | 2017 |
| CD22 | Ab | Lumoxifi | AstraZeneca | 2018 |
| UFO, FLT3 | Small molecule | Xospata | Astellas Pharma | 2018 |
| PI3Kδ / γ | Small molecule | Copiktra | Verastem | 2018 |
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References
1. Napper, A. D., & Watson, V. G. (2013). Targeted drug discovery for pediatric leukemia. Frontiers in oncology, 3, 170.
2. Wolf, D. M. C. , & Langhans, S. A. . (2019). Moving myeloid leukemia drug discovery into the third dimensiondata_sheet_1.docx. Frontiers in Pediatrics, 7.
3. Pollyea, D. A. , Gutman, J. A. , Gore, L. , Smith, C. A. , & Jordan, C. T. . (2014). Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials. Haematologica, 99(8), 1277-1284.
4. Rashkovan, M. , & Ferrando, A. . (2019). Metabolic dependencies and vulnerabilities in leukemia. Genes & Development, 33(21-22), 1460-1474.
5. Shang, Y. , & Zhou, F. . (2019). Current advances in immunotherapy for acute leukemia: an overview of antibody, chimeric antigen receptor, immune checkpoint, and natural killer. Frontiers in Oncology, 9, 917.
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