Developing Epigenetic Profiling-Based Biomarkers for Flow Cytometry, Immunohistochemistry and Liquid-ChIP Assays in Myelodyplastic Syndrome.
Jason X Cheng, Erica Kleinbrink, Jennifer Hummel, Sung-su Kim. University of Michigan, Ann Arbor
Background: The current approach for diagnosing MDS is primarily based on the morphological evaluation of a patient's peripheral blood and bone marrow cells. Although other common ancillary technologies such as flow cytometry are available, they have played little role in the clinical diagnosis of MDS due to a lack of specific markers for this disease. The lack of adequate tools in predicting the course of MDS, coupled with ineffective traditional therapies, has resulted in the majority of these patients succumbing to bone marrow failure and ∼25-30% of them developing acute leukemia. Recently, epigenetic modifying drugs such as hypomethylating agents have been shown to be a promising therapy for some MDS patients. However, no reliable biomarkers or ancillary tools are currently available to predict and evaluate their therapeutic effects.
Design: Our previous studies have revealed a gene regulatory network that controls myelopoiesis in mice. We have developed a new technology, sequential ChIP, and identified a number of genes previously unknown to be hypermethylated in MDS. Some of these, such as PU.1, SPI-B, HIC1 and EGR(s), are known to play a critical role in myelopoiesis, but have not been studied in MDS. In the current study, we have selected a small panel of signature genes based on our previous genome-wide epigenetic profiling data in MDS.
Results: We have developed clinically applicable epigenetic biomarkers for flow cytometry, immunohistochemistry and liquid ChIP based on genome-wide epigenetic profiling data in MDS. We have explored the use of epigenetic profiling-based markers and ancillary tools in the clinical diagnosis, prognosis and therapeutic management of MDS. In addition, we have also investigated the role of these signature genes such as PU.1, HIC1 and EGR(s) in the pathogenesis of MDS.
Conclusions: Epigenetic biomarkers and the epigenetic-based ancillary technologies are promising tools to assist the clinical diagnosis of MDS and to monitor the epigenetic therapies of MDS patients.
Monday, February 28, 2011 1:00 PM
Poster Session II # 177, Monday Afternoon