ASH Clinical News Advances in Hematology Research & Patient Care: Hi | Page 11

ASH 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
Jill Johnsen, MD
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 nextgeneration, 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, [