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Protein-coding genes and long noncoding RNAs are differentially expressed in dasatinib-treated chronic myeloid

Rosana A Silveira, Angela A Fachel, Yuri B Moreira

    Hematology (Amsterdam, Netherlands)
    |May 17, 2013
    PubMed

    Insights

    This study investigated molecular pathways in chronic myeloid leukemia (CML) patients resistant to dasatinib. It identified novel gene and long noncoding RNA (lncRNA) expression changes potentially driving dasatinib resistance in CML.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genomics

    Background:

    • Dasatinib is effective for imatinib-resistant chronic myeloid leukemia (CML).
    • Some CML patients develop resistance or intolerance to dasatinib, necessitating further research into resistance mechanisms.

    Purpose of the Study:

    • To identify molecular pathways and regulatory elements involved in primary dasatinib resistance in chronic myeloid leukemia (CML).
    • To analyze gene and long noncoding RNA (lncRNA) expression profiles in CML patients before and after dasatinib treatment.

    Main Methods:

    • Gene expression profiling of mononuclear cells from 7 imatinib-resistant CML patients using Agilent microarrays.
    • Analysis included protein-coding genes and long noncoding RNAs (lncRNAs).
    • Statistical analysis identified significantly differentially expressed genes and lncRNAs (fold-change >1.5; q value ≤10%) and pathway enrichment analysis (Ingenuity Pathway Analysis).

    Main Results:

    • Identified sets of significantly differentially expressed protein-coding genes and lncRNAs in CML patients after dasatinib treatment.
    • Pathway analysis revealed enriched functions, canonical pathways, and gene networks associated with differential gene expression.
    • lncRNAs were implicated alongside protein-coding genes in potential regulatory roles in dasatinib resistance.

    Conclusions:

    • Novel gene and lncRNA expression profiles are associated with dasatinib resistance in CML.
    • These findings suggest new regulatory elements, including lncRNAs, may play a role in the development of dasatinib resistance in CML.
    • Further investigation into these molecular pathways could inform future therapeutic strategies for CML.
    Keywords:
    Chronic myeloid leukemiaDasatinibImatinibLong ncRNAsResistance

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