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This section gives an overview of the disease, and where available shows the following:
More information can be found in the help pages.
✖Disease ID: | 34 | |
Name: | Acute myeloid leukemia | |
Associated with: | 6 targets | |
3 immuno-relevant targets | ![]() |
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5 immuno-relevant ligands |
Click on the target name to link to its detailed view page
Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.
If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page
Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.
More information can be found in the help pages.
✖FZD8 | |
References: | 15 |
KIT proto-oncogene, receptor tyrosine kinase | |||||||||||
Comments: | KIT mutations have been identified in founding clones from AML patients, which suggests that KIT mutations initiate development of AML. | ||||||||||
Ligand interactions: |
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fms related receptor tyrosine kinase 3 | ||||||||||||||||
Role: | Internal tandem duplications and/or insertions in the FLT3 gene are implicated in 20-25% of all acute myeloid leukemias and rare cases of acute lymphoblastic leukemia (ALL). Such FLT3 length mutations (FLT3-LM, a.k.a. FLT3-ITD, FLT3 internal tandem duplication) correlate with poor prognosis and a high relapse rate. | |||||||||||||||
Comments: | Somatic mutations in FLT3 have been found in cases of AML Idenification of FLT3 mutations in subclones of AML patient-derived cells, suggests that these may be cooperative mutations that drive established AML clones, rather than being disease initiating mutations. | |||||||||||||||
References: | 6 | |||||||||||||||
Ligand interactions: |
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Janus kinase 2 |
KRAS |
isocitrate dehydrogenase (NADP(+)) 1 | |||||||||||
Comments: | Mutant IDH1 isoforms are found in 6 to 10% of cases of AML and in a variety of solid tumours, and make these tumours susceptible to IDH1 inhibitor therapy. | ||||||||||
Ligand interactions: |
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Click ligand name to view ligand summary page
Click the arrow in the final column to expand comments
More information can be found in the help pages.
✖Key to terms and symbols | Click ligand name to view ligand summary | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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1. Birendra KC, DiNardo CD. (2016) Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120. Clin Lymphoma Myeloma Leuk, 16 (8): 460-5. [PMID:27245312]
2. Brewin J, Horne G, Chevassut T. (2013) Genomic landscapes and clonality of de novo AML. N Engl J Med, 369 (15): 1472-3. [PMID:24106951]
3. DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA et al.. (2018) Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med, 378 (25): 2386-2398. [PMID:29860938]
4. Gallogly MM, Lazarus HM, Cooper BW. (2017) Midostaurin: a novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis. Ther Adv Hematol, 8 (9): 245-261. [PMID:29051803]
5. Gou H, Zhou J, Ye Y, Hu X, Shang M, Zhang J, Zhao Z, Peng W, Zhou Y, Zhou Y et al.. (2016) The prevalence and clinical profiles of FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations in a cohort of patients with de novo acute myeloid leukemia from southwest China. Tumour Biol, 37 (6): 7357-70. [PMID:26676635]
6. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, Asou N, Kuriyama K, Jinnai I, Shimazaki C et al.. (1999) Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood, 93 (9): 3074-80. [PMID:10216104]
7. Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, Stone I, Ryan MC, Sussman D, Lyon RP et al.. (2013) SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood, 122 (8): 1455-63. [PMID:23770776]
8. Lemieux RM, Popovici-Muller J, Travins J, Cai Z, Cui D, Zhou D. (2013) Therapeutically active compounds and their methods of use. Patent number: WO2013107291. Assignee: Agios Pharmaceuticals, Inc.. Priority date: 19/01/2012. Publication date: 25/07/2013.
9. Linos K, Tafe LJ. (2018) Isocitrate dehydrogenase 1 mutations in melanoma frequently co-occur with NRAS mutations. Histopathology, 73 (6): 963-968. [PMID:30003571]
10. Ma T, Zou F, Pusch S, Xu Y, von Deimling A, Zha X. (2018) Inhibitors of Mutant Isocitrate Dehydrogenases 1 and 2 (mIDH1/2): An Update and Perspective. J Med Chem, 61 (20): 8981-9003. [PMID:29847930]
11. Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE. (2007) FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood, 110 (4): 1262-70. [PMID:17456725]
12. Miller CA, Wilson RK, Ley TJ. (2013) Genomic landscapes and clonality of de novo AML. N Engl J Med, 369 (15): 1473. [PMID:24106950]
13. Morizane C, Ueno M, Ikeda M, Okusaka T, Ishii H, Furuse J. (2018) New developments in systemic therapy for advanced biliary tract cancer. Jpn J Clin Oncol, 48 (8): 703-711. [PMID:29893894]
14. Sidaway P. (2018) Ivosidenib effective in IDH1-mutant AML. Nat Rev Clin Oncol, 15 (8): 472. [PMID:29925981]
15. Sonnet M, Claus R, Becker N, Zucknick M, Petersen J, Lipka DB, Oakes CC, Andrulis M, Lier A, Milsom MD et al.. (2014) Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia. Genome Med, 6 (4): 34. [PMID:24944583]
16. Weisberg E, Boulton C, Kelly LM, Manley P, Fabbro D, Meyer T, Gilliland DG, Griffin JD. (2002) Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell, 1 (5): 433-43. [PMID:12124173]
17. Zhao Q, Manning JR, Sutton J, Costales A, Sendzik M, Shafer CM, Levell JR, Liu G, Caferro T, Cho YS et al.. (2018) Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors. ACS Med Chem Lett, 9 (7): 746-751. [PMID:30034612]