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Characterization of epigenomic programs underlying the development B cell leukemia and lymphoma


Meena Kanduri

Contact Information | List of Publications

Aberrant DNA methylation has been implicated to play a stronger role in tumorigenesis and is associated with tumor aggressiveness and inferior outcome in various cancer types. Consequently, using de-methylating agents such as 5-aza-deoxycytidine as treatment options is currently under investigation for hematological malignancies. Alongside DNA methylation, histone modifications are the other well-studied epigenetic marks implicated in many leukemia and cancers. Histone modifications have been shown to regulate DNA methylation of many cancer related genes. Silencing histone modifications (H3K9me3 and H3K27me3) are generally coupled with DNA methylation for long term gene silencing and hence we could expect that along with the distinct methylation profiles, these entities may also contain specific histone modification patterns that are unique for each disease or within the prognostic subgroups.
My current research is focused on unraveling various kinds of epigenetic modifications mainly in chronic lymphocytic leukemia (CLL) and Mantle cell lymphoma (MCL). CLL is the most common adult leukemia in Western world and characterized by clonal proliferation and accumulation of long-lived neoplastic B-cells. CLL is a biologically and clinically heterogeneous malignancy with varying clinical course, and yet remains as incurable disease. MCL is considered one of the most aggressive lymphoid neoplasms, with poor responses to conventional chemotherapy and relatively short survival and is characterized by the t(11;14)(q13;q32) translocation.
Recent advancements in global analyses methods enable us to identify epigenetically regulated genes with prognostic and therapeutic values. Since epigenetic changes are reversible and are being aggressively pursued for therapeutic interventions, characterizing in detail the role and mechanism of these global epigenetic changes in well characterized prognostic sub-groups of CLL and MCL is very important. My research mainly applies next generation sequencing techniques like Me-DIP sequencing, ChIP-sequencing and 450K high-resolution DNA methylation arrays. We employ pyrosequencing, bisulfite sequencing, quantitative RT-PCR and protein expression analysis to characterize the genes that show differential epigenetic marks in different prognostic subgroups. By employing state of the art technologies we hope to find novel biomarkers and targets for diagnosis, prognosis and prediction of response to drug therapy.
 

List of selected publications

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-02-26
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