| Autor: |
McCoy, Matthew, Rao, Shruti, Cosgrove, Shannon, Madhavan, Subha, Kulkarni, Shashikant, Xu, Xinjie, Kanagal-Shamanna, Rashmi |
| Zdroj: |
Blood; November 2020, Vol. 136 Issue: 1, Number 1 Supplement 1 p42-43, 2p |
| Abstrakt: |
Venetoclax is an oral, highly selective, BCL2 inhibitor approved by the FDA for use in chronic lymphocytic leukemia/small lymphocytic lymphoma and acute myeloid leukemia. Despite favorable responses, multiple biological mechanisms lead to treatment resistance. One such mechanism includes somatic mutations in the BCL2gene. Multiple lines of evidence suggest that hot-spot mutations in BCL2such as Gly101Val induce treatment resistance by disrupting the binding of BCL2 to the BCL2 inhibitors such as venetoclax. Further, widespread use of high-throughput NGS technologies has identified multiple BCL2mutations and additional concurrent molecular alterations at various variant allele frequencies in patients with progression while undergoing venetoclax therapy. In order to understand and determine the clinical significance of each of these mutations, careful expert curation and integration into somatic variant annotation AMP/ASCO/CAP guidelines is needed. Further, curation of those somatic variants that may not have sufficient functional evidence in literature may benefit from additional tools such as in silicoanalysis. |
| Databáze: |
Supplemental Index |
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