Weigang Tong, Guillermo
Garcia-Manero
Department of Leukemia, The University of
Texas MD Anderson Cancer Center, Houston, TX 77030
Chronic
lymphocytic leukemia (CLL) is a heterogenous lymphoid malignancy that frequently
exhibits genetic alterations such as chromosomal translocations. In addition,
epigenetic modifications such as aberrant DNA methylation are also frequently
detected in CLL, with consequent silencing of the tumor suppressor genes. The
role of these epigenetic changes in facilitating leukemic transformation is
unclear. In the current study, we hypothesize that aberrant CpG island
methylation in CLL is correlated with inactivation of tumor suppressor genes and
this epigenetic alteration plays a key role in the molecular pathogenesis and
prognosis of CLL. To test these hypotheses, we propose the following specific
aims 1) Genome-wide screening for promoter-associated CpG islands and discover
genes that specifically methylated in CLL. 2) Determine the methylation profiles
of candidate genes in CLL patients and healthy controls; assess the prognostic
significance of aberrant methylation in CLL. 3) Develop clinical trials based on
information derived from above aims using hypomethylating agents in individuals
with CLL. Our goals are to understand the molecular mechanism of aberrant DNA
methylation and their roles in leukemogenesis. Through this study, we want to
identify new molecular markers and targets for prognosis, diagnosis and
treatment of CLL.