Identification of biomarkers to novel therapies in Myelodysplasia
The haematopoietic stem cell (HSC) malignancy myelodysplasia (MDS) is incurable with existing drug therapies. The pathogenesis and progression of MDS is due to acquired molecular and cytogenetic defects in HSC proliferation and differentiation. In addition responses by, and defects in, immunity to the MDS clone(s) shapes the clinical manifestations of MDS. The increasingly applied therapies of immunomodulatory drugs and azacitidine have pleiotropic effects modifying both HSC gene regulation and immunity leading to clinical responses. Despite initial efficacy, these therapies eventually fail and all patients progress or relapse with rapidly fatal results.
We have shown that even in patients who achieve complete remission to lenalidomide, residual abnormal bone marrow colonies persist and likely represent the source of MDS resistance and progression. Through prospective tissue banking of samples in three clinical trials for MDS undertaken at our centers we now have the opportunity to undertake a detailed biomarker analysis in MDS which has never before been attempted.
We are currently undertaking a detailed analysis of immunology and gene expression profiles in bone marrow and peripheral blood samples prior to therapy to identify pre-treatment profiles that predict for patient response to treatment.
- Dr Rachel Koldej, Senior Scientist
- Dr Lynette Chee, Consultant Haematologist and VCA Fellow
- Mrs Mandy Ludford-Menting, Research Assistant
- Dr Melita Kenealy, Cabrini Health
- Dr Michael Dickinson, Peter MacCallum Cancer Centre
- Fight Cancer Foundation
- Victorian Cancer Agency
- Royal Melbourne Hospital Foundation
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