By Drs. Ghia and Smith
Chronic Lymphocytic Leukemia (CLL) is a disease that causes uncontrollable growth of body’s white blood cells, called B-lymphocytes or B cells. Patients with aggressive disease experience a rapid increase in white blood cells counts over a relatively short period of time and will require treatment soon after diagnosis. On the other hand, in patients with indolent disease, the rise white blood cell counts occurs more slowly. Unfortunately, indolent forms of CLL invariably transition to aggressive CLL, necessitating treatment. Understanding this transition from indolent to aggressive disease, known as CLL progression, is one Emanuela Ghia, Ph.D.’s primary research interests.
Dr. Ghia, an Assistant Project Scientist in Dr. Thomas Kipps’ laboratory, has been researching the mechanisms that drive the progression of CLL, collaborating with Erin Smith, Ph.D., from the Genome Information Sciences Division, led by Kelly Frazer, Ph.D., at the UC San Diego Moores Cancer Center. More specifically, they are working to identify the genetic and epigenetic changes that drive CLL progression.
What are genetic and epigenetic changes?
Genetic changes are mutations that occur in DNA. Interestingly, depending on their location and type, some mutations may have no negative consequences on our health while others can facilitate cancer growth. For example, in CLL some mutations may accelerate the growth of B-lymphocytes. Epigenetic changes are due to alterations in what genes are actually expressed. Such control of gene expression allows for different cell types, such your as skin cells or blood cells, to have striking differences in what proteins they use even though both have the same blueprint DNA, which codes for these proteins. An important process that turns on or turns off genes is called “methylation”.
Drs. Ghia and Smith are evaluating leukemia cells from patients who progressed from indolent to aggressive disease and required treatment. Leukemia cells are collected at two time points: (1) within 1 year from diagnosis and (2) after 4 or more years from diagnosis and within 1 year of requiring therapy. The collection of these leukemia cells allow Drs. Ghia and Smith to perform whole-genome sequencing* to study genetic changes and to perform methylation analyses** to study epigenetic changes.
This study is designed to allow researchers in the field of CLL to understand the genetic and epigenetic changes that are the key players driving CLL progression. Moreover, this important study should provide hope for patients with CLL because it will enable the development of new therapies specifically designed to target the genetic and epigenetic changes determined to play an important role in CLL progression.
*Whole-genome sequencing is an efficient method to selectively sequence the coding regions of the genome and also to calculate allele frequency. Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein. In the human genome there are about 180,000 exons: these constitute about 1% of the human genome, which translates to about 30 megabases (Mb) in length.
**DNA methylation array is designed to interrogate whether known DNA CpG islands are methylated or not. CpG islands are genomic regions that contain a high frequency of cytosine and guanine next to each other. DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression.
Drs. Ghia and Smith are working with the UC San Diego’s Moores Cancer Center “My Answer to Cancer” Program**. This initiative is working to pinpoint the root cause of several cancers, ranging from chronic lymphocytic leukemia to breast.
The UC San Diego Moores Cancer Center is poised to implement genomic sequencing and personalized care for all of our patients and transform the way we treat cancer. Sharing space with researchers and clinical trials means that the Moores Cancer Center can quickly deliver new discoveries from the laboratory to our patients. Simply put, UC San Diego Moores Cancer Center is the perfect place for the MY ANSWER TO CANCER initiative. Please visit “My Answer to Cancer” at http://cancer.ucsd.edu/mac/ to learn more about this initiative.