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© 2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Whereas lenalidomide is an effective therapy for del(5q) MDS patients, a minority of non-del(5q) MDS patients achieve hematologic improvement with lenalidomide. We used computational biology modeling and digital drug simulation to examine genomic data from 56 non-del(5q) MDS patients treated with lenalidomide, and then matched treatment response with molecular pathways. The computer inferred genomic abnormalities associating with lenalidomide treatment response in non-del(5q) MDS to include trisomy 8, del(20q), or RUNX1 loss of function mutations. Genomic abnormalities associating with lenalidomide resistance in non-del(5q) MDS patients included mutations in SF3B1, TET2, WNT3A amplification, MCL1 amplification, and/or PSEN2 amplification. These results may inform protocols for determining appropriateness of lenalidomide in non-del(5q) MDS.

Details

Title
Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes
Author
Drusbosky, Leylah M; Cogle, Christopher R  VIAFID ORCID Logo 
First page
3323
Publication year
2020
Publication date
2020
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2402168279
Copyright
© 2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.