All living things--from dandelions to reindeer--evolve over time. Cancer cells are no exception, and are subject to the two overarching mechanisms described by Charles Darwin: chance mutation and natural selection.

In new research, Carlo Maley, PhD., and his colleagues describe compulsive evolution and dramatic genetic diversity in cells belonging to one of the most treatment-resistant and lethal forms of blood cancer: acute myeloid leukemia (AML). The authors suggest the research may point to new paradigms in both the diagnosis and treatment of aggressive cancers, like AML.

Maley is a researcher at Arizona State University's Biodesign Institute and an assistant professor in ASU's School of Life Sciences. His work focuses on applying principles of evolutionary biology and ecology to the study of cancer.

The group's findings appear in this week's issue of the journal Science Translational Medicine.

The cells, they are a changin'

A tumor is a laboratory for evolutionary processes in which nature experiments with an immense repertoire of variants. Mutations that improve a cell's odds of survival are "selected for," while non-adaptive cells are weeded out in the evolutionary lottery.

Genetic diversity therefore provides cancer cells with a library of possibilities, with some mutations conferring heightened resistance to attack by the body's immune system and others helping malignant cells foil treatments like chemotherapy. Generally speaking, the seriousness of a given cancer diagnosis may be linked with genetic diversity in cancerous cells. High diversity means the cancer has many pathways for outsmarting treatment efforts.

The diagnosis of cancer and study of disease progression is often accomplished by examining a tumor sample containing many billions or even trillions of cells. These are subjected to so-called next generation sequencing, a technique that sifts the vast genetic composite, ferreting out sequence variants (or alleles) caused by mutations in genes. The process then evaluates the frequency of these alleles, using the results to chart disease progression and assess the effectiveness of treatment.

According to Maley, such methods may obscure the true degree of genetic diversity, as well as the manner in which mutations arise. "One issue here is that if a mutation occurs in less than 20 percent of the cells, it's hard to detect by modern methods," he says. For example, because individual cells in the tumor probably carry unique mutations, they would be virtually impossible to observe with standard sequencing methods.

A further issue is that tracking mutations through bulk analysis of cells is typically based on certain assumptions as to how mutations arise and what their frequencies mean.

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Cancer's relentless evolution