Translating Genetic Information to Hematologic Care: An Interview with Jill Johnsen, MD

The recent exponential growth of DNA sequencing capabilities has given hematologists unprecedented views of the human genomic landscape and, with that information, the potential to tailor care to individual patients. However, for the non-genomics expert, the prospect of translating the enormity of genomics into meaningful and clinically useful information can be daunting.

JohnsenASH Clinical News spoke with Jill M. Johnsen, MD, assistant professor of medicine in the Division of Hematology at the University of Washington School Medicine and assistant member of the Bloodworks NW Research Institute in Seattle, Washington, about the possibilities of using genetic testing to care for hematology patients. Dr. Johnsen was chair of the session “Guiding Hematologic Care with Genetic Testing” at this year’s annual meeting.

ASH Clinical News: The promise of genetically informed, personalized clinical care has seemed tantalizingly close for some time but, with recently available technologies, is this dream now more of a possibility?

Jill Johnsen, MD: We are, fundamentally, at that point. Recent advances in technology have really changed the scale at which clinicians can perform these types of molecular typing. In hematology, we have been performing genetic testing for decades through phenotyping and some very low–resolution typing.

Now, with the advent of large-scale sequencing and genetic arrays, we can take this information and bring it to the clinic.

Hematologists have an advantage because we do know what to do with this genetic information in many cases; in other fields, actionable variants are harder to identify. As a whole, I think hematology is ahead of the curve in genetics.

What are the challenges that remain with DNA sequencing?

One of the biggest challenges is translating language from the genetics field into language that a hematologist can understand and take action on – and convey to patients. We may all talk about the same thing, but use different terminology. We need to establish a common, unifying language.

Hematology has its own dictionary of terms, so trying to explain everything isn’t easy, especially given the many subsets of disciplines within our field. As geneticists, we need to be able to convey what it is we have found in the DNA, what we think it means, and the uncertainties that may exist.

How is next-generation sequencing affecting the use of genetic testing in hematologic care?

With next-generation sequencing, or high-throughput sequencing, we can perform DNA sequencing on a large scale at a lower cost. The costs have lowered to a point where we can start using these tests for clinical purposes. Targeted sequencing, where we can focus the sequencing reads on a small panel of genes, speeds up the process, as well. With the costs shrinking and the scale growing, we can do many more interesting things with structural variations now than we have ever been able to do before.

Next-generation sequencing means we are able to assay many variants and many regions of the genome at the same time, whereas previously, we had to look for a single variant without knowing what other modifying variants might be around.

Fortunately, the next-generation assays are being developed through academic and industry partnerships and are currently moving through the U.S. Food and Drug Administration’s approval process. If approved, these tests could be implemented in the clinical lab. That’s why we need to start the conversation now about what these results will mean in practice.

During the session, you mentioned the possibilities of clinical applications of targeted gene sequencing, but also the ethical and social considerations of diagnosing disorders via gene sequencing. Can you discuss those more?

By performing targeted sequencing, we can focus on the question we want to ask; in some ways, it liberates us from discovering incidental findings and finding uncertain answers to questions we did not ask. Nevertheless, we need to understand how to counsel people on the results of genetic testing. These have important implications for patients, as well as family members who might be at-risk to be carriers of these mutations.

Take sickle cell trait for example: When a patient is found to have sickle cell trait on DNA sequencing, it does not mean that he or she has sickle cell disease, but there are still significant considerations in returning those results to the patient and his or her family.

The delivery of sickle cell trait information – particularly in communities where genetic information is not commonly disseminated or there are other social issues – is a very important conversation to have in the hematology community. It also sets the template for how we should return results for conditions with similar clinical implications.

When do you think we will see these newer genetic testing methods used routinely in clinical practice?

It’s always an evolution. We have been using arrays in clinical practice for a long time, and we are starting to use next-generation, targeted sequencing in the clinic now. At this point, we are focusing on how to partner clinical questions with the right tests. All of these tests have different capabilities and all are evolving very rapidly, so we need to make sure that we are asking thoughtful questions of DNA.

We then need to take advantage of the discoveries that are made from looking at the whole genome and adjust how we ask these questions going forward. It’s an iterative process that we are in the middle of right now.

It is an exciting time in genetics and hematology. We’ve opened the lid and we’re shining a light inside, hoping to bring that information into the light. It is unfamiliar, though, so we need to take that information and make it not scary, so to speak. By creating a shared language for clinicians, patients, and families and communities we can finally start to understand what these genetic variants are, what they do, and what they mean.