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Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes.

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.

SUBMITTER: Drusbosky LM

PROVIDER: S-EPMC7246771 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes.

Drusbosky Leylah M LM Cogle Christopher R CR

International journal of molecular sciences 20200508 9

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 tris ...[more]

PMID: 32397113

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