Unknown,Transcriptomics,Genomics,Proteomics

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Whole exome sequencing of human MDS/AML OCI-M2 and patient-derived bone marrow cell lines treated with 5-azacytidine


ABSTRACT: The whole exome sequencing experiment is part of the study: “Analysis of 5-azacytidine resistance models reveals a set of targetable pathways”. In the study we generated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) OCI-M2 cell lines as well as patient-derived bone marrow cell lines that are resistant to hypomethylating therapy by 5-azacytidine (AZA). By integrated analysis of expression and mutation data obtained from these samples we have identified multiple signaling pathways whose modulation by specific small molecule inhibitors significantly block proliferation of AZA-resistant cell lines without increasing their sensitivity to AZA. The understanding of the molecular mechanisms which characterize the AZA-R phenotype can be used for broadening therapeutic options at progressing states during AZA therapy.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Juraj Kokavec 

PROVIDER: E-MTAB-11172 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


The mechanisms by which myelodysplastic syndrome (MDS) cells resist the effects of hypomethylating agents (HMA) are currently the subject of intensive research. A better understanding of mechanisms by which the MDS cell becomes to tolerate HMA and progresses to acute myeloid leukemia (AML) requires the development of new cellular models. From MDS/AML cell lines we developed a model of 5-azacytidine (AZA) resistance whose stability was validated by a transplantation approach into immunocompromise  ...[more]

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