PedAM
Pediatric Disease Annotations & Medicines
| Disease | lymphoma |
| Phenotype | C0027819|neuroblastoma |
| Sentences | 2 |
| PubMedID- 24367637 | Mutations of a682, a buried residue found at the terminus of β-6, have been identified in cases of lymphoma (a>g)[27,33], ws with neuroblastoma (a>t)[21], and aml (a>v)[29]. |
| PubMedID- 23935373 | In neuroblastoma, frequent point mutation of the rtk anaplastic lymphoma kinase (alk) in the kinase domain (f1174l) leads to constitutive activation of stat3.50 forced expression of this mutant, but not wild-type alk, is sufficient to transform ba/f3 cells, enables cytokine-independent growth, and confers sensitivity to the small molecule alk inhibitor tae684 in neuroblastoma cell line models.50 further, in alk-positive anaplastic large-cell lymphoma cells that overexpress stat3, inhibition of alk leads to downregulation of total and active stat3.51 similar results have been found for other kinase domain mutations, including the well-studied jak2 mutation v617f, which is primarily found in myeloproliferative disorders.52,53 activation of jak2 caused by this mutation leads to constitutive activation of stat3 and is associated with reduced survival in idiopathic myelofibrosis.54,55 another mechanism of kinase-driven stat3 activation in cancer is genomic amplification of kinase genes or rtk ligands with subsequent protein overexpression, leading to enhanced activation of wild-type kinases. |
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