UCSB chemistry and biochemistry professor Norbert Reich and his team of researchers have recently discovered a molecular pathway that may explain the way acute myeloid leukemia develops.
AML is a cancer that occurs inside the bone marrow and destroys healthy blood cells. Eventually, patients become more susceptible to infections and prone to bleeding due to the decrease in the number of normal red and white blood cells as well as platelets.
According to Reich, a mutation in the protein DNMT3A affects the translation of DNA. DNMT3A encodes DNA methyltransferases — enzymes that catalyze the addition of a methyl group to the cytosine residues of CpG dinucleotides. This is the site where cytosine, one of the main bases found in DNA and RNA, can be methylated, or “tagged,” to turn on or off a certain gene. In AML patients, there is a mutation that disrupts the four proteins involved in tagging.
Reich’s research on DNA methyltransferases coincided with another group’s similar medical research regarding AML.
“It just happened to be that the enzyme we were studying applied to AML patients,” Reich said. “DNMT3A is not specific to just AML.”
Since it is involved in mammalian development, the mutations of DNMT3A are also applicable to other types of cancers. Overexpression of this protein has been reported in numerous studies on malignancies including prostate, colorectal and breast tumors.
The team’s research is based on the theory of epigenetics, the study of changes in gene activity that do not involve alterations in the genetic code but are still passed down to at least one successive generation. Every cell in the body has the same DNA yet differs in its epigenome, or tagging pattern. This difference allowed Reich to make the connection between the disrupted tagging pattern and its prevalence in leukemia patients. Upon observing this phenomenon, Reich proposed treating cancer using new methods rather than embracing the traditional “one-fits-all” chemotherapy.
Reich used rats to observe applied epigenetics and observed how a mother rat’s grooming and nursing methods could affect the long-term behavior of her offspring.
“We’ve all heard that the way your mother treats you when you’re younger shapes how you are when you’re older,” Reich said. “But this is the chemistry behind that phenomenon.”
These effects can be correlated with DNA methylation. Epigenetics may be seen as the convergence of the nature versus nurture theory.
“We’re talking about change within one generation,” Reich said. Epigenetics is based on the idea that environmental stressors can elicit a biological response that can be inherited through successive generations. If the environmental stressor is removed, however, the epigenetic marks will eventually fade and revert back to the original DNA programming.
Despite the potential this epigenetics research has for better cancer treatment, a final analysis of the research’s findings and their applicability has yet to be definitively determined.