By Karen Ring

The risk of getting cancer increases as you age due to multiple somatic mutations (meaning that you acquire the mutation rather than are born with it) that build up in certain cell populations over time. Hematological cancers, also known as “blood cancers” or “liquid tumors”, affect the blood, bone marrow, and lymph nodes. Examples of hematological cancers include leukemia (abnormal white blood cells), lymphoma (abnormal lymphocytes), and myeloma (abnormal plasma cells).

Diagnosing blood cancers is relatively easy. Doctors can take blood samples from sick patients (instead of conducting invasive tumor biopsies) and look for abnormal cancer cells in the blood or genetically screen for cancer causing mutations. Already, scientists have identified numerous genes and mutations that may contribute hematological cancers. However, mutations in multiple genes are usually required to override the body’s natural immune response against cancer. Age-related clonal hematopoiesis is also a culprit for increasing risk of blood cancer. Clonal hematopoiesis is the idea that as hematopoietic stem cells age, they can acquire somatic driver mutations and the resulting clonal expansion populations have an increased likelihood of acquiring further mutations that can cause cancer later in life (See Figure 1).

Clonal expansion can lead to hematological cancer when hematopoietic stem cells that acquire early somatic driver mutations later acquire additional cancer-causing mutations.

Figure 1. Clonal expansion can lead to hematological cancer when hematopoietic stem cells acquire early somatic driver mutations and later acquire additional cancer-causing mutations.

As with other cancers, the risk for getting blood cancers increases as you age. In fact, it’s been reported that around 2% of elderly people over the age of 75 have large chromosomal abnormalities that put them at risk for blood cancers. Currently, there is no predictive test to determine whether a healthy individual will get hematological cancer later in life. However two separate studies led by Steven McCarroll at Harvard Medical School and Benjamin Ebert at Brigham and Women’s hospital recently addressed this issue by looking for cancer risk factors in thousands of blood samples from young and old people that had not been previously diagnosed with blood cancer. Their results were published together in the New England Journal of Medicine last week.

Both groups reasoned that clonal hematopoiesis typically precedes cancer-causing chromosomal abnormalities. Therefore they surmised that identifying genes in which driver mutations cause clonal expansion could be useful in predicting who will get blood cancers later in life. To make a long story short, both groups found that older people had a higher chance (10% of people older than 65) of having a somatic driver mutation that could cause blood cancer compared to younger people (only 1% of those under 50). Further genomic analysis of clonal expansions from both studies determined that somatic mutations were found most frequently in the genes DNMT3A, TET2, and ASKL1. All three genes have been previously associated with hematological cancers. Because both studies had access to patient medical records, they also determined that having a somatic driver mutation significantly increased your risk of getting hematological cancer, and also elevated your risk of heart disease, stroke, and even death.

While results from these studies suggest that regular genomic screening of blood samples could enable early detection of blood cancers, both groups believe this idea to be premature. They point out that while 10% of elderly people have clonal hematopoiesis with somatic mutations, only 1% of these patients per year actually get cancer. Therefore these studies suggest that technologies should be further developed to identify “at risk” individuals by identifying clonal expansions and somatic driver mutations and to potentially prevent the onset of hematologic cancers.