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Brunangelo Falini, Professor of Haematology, University of Perugia, Italy

Patients with acute myeloid leukaemia (AML)
and hairy cell leukaemia (HCL) are more likely
to receive appropriate, effective treatments
today than they were a decade ago, thanks
to important advances in our understanding
of the conditions at a molecular level. The
identification of some of the key genetic
variations underlying different forms of these
blood cancers have allowed better targeting of
existing therapies and provided the foundations
for the development of new treatments.
Brunangelo Falini is widely recognized
as having led this scientific charge. On 6
May 2015 he received the prestigious French
ARC Foundations Leopold Griffuel Award
for translational and clinical research at
a ceremony in Paris in recognition of his
achievements. Here, he reveals what has driven
his quest to better understand and treat these
diseases, and explains how caring for patients
inspires his research and vice versa.

dierent gene variant combinations can help

doctors determine whether the best treatment
is chemotherapy on its own or transplantation
of stem cells that generate healthy blood cells,
which can cure those with poor prognosis but
carries a high mortality risk.

Q: What was your major contribution to

HCL research?
Although it had long been possible to
recognize the unusual shape of HCL cells
under the microscope, their underlying genetic
characteristics remained a mystery for over
half a century. In 2011 we used whole exome
sequencing to nd ve genetic mutations present
in a patients HCL cells but not in their healthy
ones. Among them was a BRAF mutation that
was already implicated in melanomas and
we found it to be present in all 48 HCL cases
checked. Later validation points to it being the
disease-dening genetic lesion of HCL.
Patients with HCL can usually be diagnosed
under the microscope, but there are other
Q: Could you describe your key
leukaemias and lymphomas that resemble it.
breakthrough in AML research?
We found that the BRAF mutation is, with rare
About 15 years ago we observed that in
exceptions, specic to HCL among lymphomas,
about 30% of AML cases, a protein called
so in 2012 we developed the rst molecular test
nucleophosmin (NPM1) appeared not to be
for the condition. ats important because
expressed in the cell nucleus as we expected
there are drugs called purine analogues that
but, surprisingly in the cytoplasm . These were
AML with normal cytogenetics patients - those are quite eective for HCL, but not for other
blood cancers that can mimic it. Last year
in which you could not nd abnormalities
we completed a phase II trial using the BRAF
with cytogenetic techniques for examining
inhibitor Vemurafenib for 28 patients for whom
chromosomes. This was before the widespread
standard therapies had failed. We had benecial
availability of whole genome sequencing,
however we were able to sequence single genes, responses in all but one patient, with complete
and therefore were able to identify the mutation remission in about 35% of participants and partial
remission in 61%.
in the NPM1 gene responsible for causing
this type of AML. In 2008 the World Health
Organisation recognized NPM1-mutated AML as Q: Does research or clinical work give you
a new form of leukaemia.
the most satisfaction?
For me the two are inseparable. It is not only
about going from the bench to the patient, but
Q: How has this advance helped
these patients?
also from the patient to the bench. Because I
AML patients are treated based on clinical
have spent time investigating the morphological
parameters, but especially according to
features and genetic alterations of lymphomas
molecular alterations of leukaemia cells. We now and leukaemias, I am better able to categorize
know that having the NPM1 mutation can give
my patients cancers, understand their disease
patients a more favourable prognosis depending progression and determine the best therapeutic
on what versions of another gene they have. The strategy. Im also constantly brought face-to-face
denition of NPM1-mutated AML as a separate with the reality that many patients still succumb
condition and understanding the eects of
to their leukaemias and lymphomas, and this

provides the strongest possible motivation for

my research and translation eorts. Clinical
observations have led me to investigate specic
things and helped me understand that, in
addition to developing new drugs, we should
also re-think old drugs in the light of the new
genomics knowledge.

In addition to developing
new drugs, we should
also re-think old drugs
in the light of the new
genomics knowledge.

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Q: What inspired your career choices?

In 1908 my great-grandfather Undecimo
Bindocci, who was a chemist and pharmacist,
won a gold medal at an international exposition
also in Paris for his invention of the eervescent
laxative. I did not meet him but my parents
often talked of his creativity. His medal still
hangs on the wall of the family pharmacy run
by my brother in Perugia. My grandfather was
a veterinarian, and both my grandmother and
father were pharmacists, so science was often
in the air in our family. Another major inuence
was that from adolescence, for reasons I cannot
explain, I was afraid of getting sick and being
destroyed by cancer, while also being extremely
curious about the mysteries underlying the
disease. My curiosity triumphed over my fears
and led me to the fascination that became my
lifes work.
Q: What does winning the Leopold Griuel
Award mean to you and how will you
spend the prize money?
When I look at the list of previous winners I
sometimes feel that I do not deserve it. Its a
real honour. It is also an opportunity because it
comes with 125,000 to promote research. AML
remains an incurable disease in 50% of patients
below the age of 60 and in 85-90% of older
patients, so although nothing has been nalized,
Id like to use this money as part of our eorts to
nd new drugs to treat it better.

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Leopold

RECRUITMENT NATUREJOBS

TH

Griffuel

awards

rewarding major breakthroughs in

CANCER RESEARCH

2 Awards of 150,000
Basic Research &
Translational and
Clinical Research

Deadline for nominations

I N F O R M AT I O N W W W. R E C H E R C H E- C A N C E R . N E T

The ARC Foundation Leopold Griffuel Awards are one of the most
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1970, the ARC Foundation honors scientists and physicians who
have made major contributions in the understanding, diagnosis,
treatment and prevention of cancers. It was established according
to Mrs Griffuels will, in honor and memory of her late husband,
Mr Leopold Griffuel.
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