Hereditary leukemia syndromes: What patients and their families should know

Certain genetic changes, or mutations, can increase a person’s chances of developing cancer. These changes, known as hereditary cancer syndromes, can be passed down from parent to child. Hereditary leukemia is one of the newest areas our experts are studying.

Courtney DiNardo, M.D., and genetic counselor Sarah Bannon with MD Anderson’s Hereditary Leukemia Clinic are among a handful of health care providers worldwide specializing in hereditary leukemia syndromes. They recently spoke with us about hereditary leukemia and what having one of these syndromes means for patients and their family members.

Here’s what they had to say.

What genes cause hereditary leukemia?

Researchers have identified about a dozen unique syndromes for hereditary leukemia, and that list is growing every year. For a long time, leukemia was thought to be sporadic and not hereditary, even though it clearly ran in some families. In 2008, one of the first genes linked to leukemia -- RUNX1 -- was identified and became available for genetic testing in 2008. People who inherit changes in the RUNX1 gene can face a higher risk of acute myeloid leukemia (AML). The RUNX1 mutation can also cause the carrier to have a lower platelet count, which plays an important role in blood clotting.

Once that gene was identified, more major research was conducted to see if there were more gene mutations linked to hereditary leukemia. These efforts have paid off. Of these dozen or so genes, about nine of them have been discovered since 2013.

We’ve found that these genes can cause different types of leukemia and related conditions, including AML, myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL).

How common is hereditary leukemia? And when do you test patients for hereditary leukemia syndromes?

We don’t know exactly. With breast cancer, we know about 5% of cases are hereditary because massive studies have tested large groups of patients and that’s what shakes out. We haven’t had a chance to do that for leukemia. At this point, we’re only testing cancer patients when there’s a reason to think the disease has been inherited or when we believe a patients’ family members are likely to have the syndrome. Based on that, it seems that at least 5% of all leukemia may be hereditary. The number among pediatric patients is likely higher.

How do doctors test for hereditary leukemia syndromes?

Genetic testing for leukemia is different than it is for solid tumors, like breast or colorectal cancers. It can’t be done on blood or saliva. It requires a skin punch biopsy, where we take a small piece of skin and connected tissue and test that. We do this procedure because with leukemia, the cancer is actually in the blood. If you tested the blood, you’d see the genetic alterations of the disease itself. We have to get a source of DNA that’s not altered by the cancer to see a leukemia patient’s inherited genes.

What treatments do patients with hereditary leukemia typically receive?

We know that certain drugs are potentially more likely to work for people with certain syndromes. The chemotherapy drug lenalidomide, for example, may be particularly effective for people with mutations in the gene DDX41. Where it makes the biggest difference is in patients undergoing a stem cell transplant. Patients with some hereditary leukemia syndromes may benefit from a different combination of medications given as part of their transplant.

In addition, these syndromes may change the screening process for potential stem cell donors. Immediate family members -- usually siblings, parents and children -- are the first people we look to when the patient needs a stem cell transplant. But those family members may have the same genetic change as the patient, which may increase the odds of transplant complications if we were to use their stem cells. So we have two rounds of testing. First, we test to see if the family member is a good donor match. If so, we test to see if the potential donor has the hereditary leukemia syndrome.

If the family member does have the same syndrome and there are no other donor options within the family, we’ll look for an unrelated donor instead. If we can’t find a match, we may end up using stem cells from the family member with the syndrome, knowing that there could be complications.

Does having one of these syndromes increase the odds of recurrence? Does it impact survivorship care?

We don’t know yet if having one of these syndromes increases the odds of leukemia relapse after a patient has gone into remission.

We do know that some hereditary leukemia syndromes increase the risk for other cancers. Dyskeratosis congenita and Fanconi anemia, for example, increase the patient’s risk for developing squamous cell carcinoma. Screening for those cancers should be part of the patient’s survivorship plan. At MD Anderson, we’ve incorporated these screenings for into the survivorship care of our hereditary leukemia patients. Not all leukemia syndromes are associated with increased risks for other types of cancer, though. Some just predispose to leukemia.

If a patient has a hereditary leukemia syndrome, what does that mean for their family members?

When a patient tests positive for one of these syndromes, in most cases there’s a 50% chance that their siblings and their children each have the same syndrome. One of their parents likely has it as well.

For these family members, we recommend genetic counseling so they can learn about their own cancer risks, cancer screenings and other health issues connected to the syndrome. Some family members may also choose genetic testing to see if they carry the genetic mutation. If they test positive for the syndrome, we strongly recommend they start a screening program that can help catch the disease in its early stages, when it is most treatable.

Since these syndromes are very new, we are looking to start screening protocols with family members who have the same syndrome but haven’t developed leukemia. By following these individuals, we can learn more about the how hereditary leukemia develops, and begin to create surveillance protocols and clinical trials to reduce carriers’ risks of developing leukemia.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.