ASH News Daily 2016 - Issue 3 - A-16

Page A-16

ASH News Daily

Monday, December 5, 2016

Genome Editing
«« From Page A-10
RN Keesha
Roach (left)
gets a hug
from Adrienne
Bell-Cors while
discussing her
poster
during the
Promoting
Minorities in
Hematology
reception on
Saturday
evening.

Convention Center). He and his colleagues performed a high-throughput small hairpin RNA (shRNA)
screen in the MLL-AF9 mouse
model that identified Phf20 as a
key epigenetic modulator. CRISPR
technology was selected for rapid
confirmation of shRNA screen results in multiple MLL-rearranged
leukemias, and they confirmed that
Phf20 knockdown synergized with
DOT1L inhibitors in these leukemias. "We have taken advantage of
a new CRISPR application to determine exactly which domains of the
Phf20 protein are critical for MLL-

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"We have taken advantage
of a new CRISPR application to determine exactly
which domains of the Phf20
protein are critical for
MLL-rearranged leukemias."
rearranged leukemias," Dr. Anderson stated. "This nominates these
domains as potential drug targets."
CRISPR-Cas9 technology can
serve an important role in targeted
disruption in vivo, especially examining combinatoric effects of
specific alterations. Today at 10:45
a.m., Dr. Sebastien Jacquelin will
describe how they used CRISPR to
disrupt DNMT3A in murine hematopoietic cells in order to study its
effect in the presence of JAK2 V617F
mutation as a model for myeloproliferative neoplasms (abstract #794;
Pacific Ballrooms 21-22, San Diego
Marriott Marquis & Marina).
Additionally, at 11:00 a.m., Dr.
Zuzana Tothova, from Dr. Benjamin Ebert's lab, will present their
group's seminal work using genome engineering in human hematopoietic stem and progenitor cells
(HSPCs) to model the serial acquisition of mutations leading to clonal
hematopoiesis, and ultimately, myeloid malignancy in a mouse xenotransplantation system. They accomplished this by using multiplex
CRISPR-Cas9 disruption in some of
the most frequently mutated genes
in myeloid malignancy to mimic
known inactivating mutations. This
technique is "highly customizable"
and "gives the additional benefit
of recapitulating genetic complexity seen in patients, studying clonal
dynamics and evolution, and most
importantly, we believe that these
models will be invaluable in studying the biology and therapeutic
vulnerabilities of specific genetic
lesions found in patients," Dr. Tothova told ASH News Daily (abstract
#741; Room 6DE, San Diego Convention Center).
While my taxi driver was ultimately right that CRISPR is not quite
ready for the clinic, older genome engineering technologies have already
demonstrated that it may soon be
possible. CRISPR, despite its drawbacks, has exploded in popularity
as evidenced by the numerous 2016
ASH Annual Meeting abstracts using this technique. Work presented
at this meeting shows that CRISPR
is a viable and promising technique
for the generation of mouse models
using human stem cells. With further
refinement in nuclease targeting and
homology-directed repair, we may
all soon be editing away.
Dr. Blachly indicated no relevant
conflicts of interest.

Table of Contents for the Digital Edition of ASH News Daily 2016 - Issue 3