ASH News Daily 2016 - Issue 2 - A-2


ASH News Daily

Page A-2

Sunday, December 4, 2016

®

ASH News Daily
2016 Editorial Board
Editor

Aaron T. Gerds,
MD, MS,
Cleveland Clinic
Taussig Cancer
Institute
@AaronGerds
Authors

James S. Blachly,
MD, The Ohio
State University
@jamesblachly

R. Frank
Cornell, MD,
Vanderbilt
University
Medical Center
@myeloma_
doc_com
Rakhi P. Naik,
MD,
Johns Hopkins
Hospital
@redcell_doc
Naveen
Pemmaraju, MD,
The University
of Texas MD
Anderson
Cancer Center
@doctorpemm
Leslie Skeith,
MD,
Thrombosis
Fellow,
University of
Ottawa,
Ottawa, Canada
@leslieskeith
Shruti Chaturvedi, MBBS,
Vanderbilt University
Medical Center, is serving as
a Junior Author this year.
©2016 by the American Society
of Hematology
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used, reproduced, or otherwise
exploited in any manner
without the expressed prior
permission of ASH News Daily.
Contributing authors have
declared any financial interest
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competing products, regardless
of the dollar amount. Any such
financial interest is noted with
the respective articles.

EPIGENETICS AND GENOMICS

Put on Your 3-D Glasses
By James S. Blachly, MD

Y

esterday the Ad Hoc Scientific Committee on Epigenetics
and Genomics held two sessions on Enhancers and Chromatin
Landscapes in Development and
Cancer. Chaired by Drs. Ash Alizadeh and Grant Challen, these sessions explored the emerging field
of 3-D chromatin structure as an
epigenetic control mechanism. Although we are used to thinking of
DNA as a linear sequence, in the
cell, it is a complex mass, tightly
packed just-so. Sunday's presenters
reminded us that we have not appreciated the incredible importance
of this packing until recently.
First up was Dr. Bing Ren, whose
work played a major role in the ENCODE project and who is a member
of the Epigenomics Roadmap and
the National Institutes of Health 4D
Nucleome Consortium. Leveraging
this expertise, Dr. Ren presented unpublished novel findings and techniques to study the 3-D genome.
Dr. Ren explained that "although we
have understood for a long time that
cis-regulatory elements play an important role in controlling gene expression, there has been an explosion
of knowledge in the last few years related to long-range control elements,
which are able to exert their influence
by being brought into proximity to
genes in 3-dimensional space." Using modern techniques like capture
Hi-C, Dr. Ren and others have been
able to "identify promoter-centered
chromatin interactions for more than
21 human tissues and cell types."
This unpublished work, when complete, will be an invaluable atlas of
long-range interactions and, "most
importantly, we can use this map to
annotate noncoding variants that are
associated with human disease." He
concluded by introducing a brandnew technique, proximity ligation
assisted ChIP sequencing, or PLACseq, that could generate a huge savings in time and cost compared to
the current gold standard, Hi-C.
Acute myeloid leukemia (AML)
was the first cancer to have its genome sequence comprehensively
studied, and now, experts such as
Dr. Ioannis Aifantis are working to
unlock more secrets of the AML genome by examining how its unique
combination of 3-dimensional structure plus mutations in epigenetic
factors including cohesins - proteins that help maintain 3-D structure - as well as a less well-studied
factor, MED12. He presented unpublished work on the remarkably
specific role MED12 plays in hema-

topoietic cell development as well
as maintenance of long-term hematopoietic stem and progenitor cells.
Dr. Aifantis indicated that "our
challenge now is to translate specific mutations in epigenetic factors to
changes in 3-D chromosomal topology and effects on cellular transformation." See abstracts #1708, #1564,
#3182, and #2903, which deal directly with individual members of the
cohesin complex.
Dr. Ravi Majeti closed the session by describing experiments
projecting leukemia into the order
of normal development on the basis of chromatin accessibility. He
described recently published work
in which his group profiled individual elements of the hematopoietic hierarchy with both ATAC and
RNA sequencing. "The hematopoietic system provides a perfect opportunity to explore chromatin accessibility because all of these cells
can be derived by cell sorting, and
paired ATAC-seq and RNA-seq
profiles of the hematopoietic hierarchy provides a rich resource for
the study of AML." By then drilling down to the single cell level,
Dr. Majeti has been able to investigate chromatin accessibility in
leukemogenesis, showing that patients' leukemias have regulatory
contributions from different stages
of development, not only at the
population level, but remarkably,
within individual cells as well! He
concluded by telling us, "chromatin accessibility provides insights
into both normal hematopoiesis
and disease biology and is an ideal
tool to understand development."

Dr. Iannis Aifantis presents his
findings during "Enhancers and
Chromatin Landscapes in
Development and Cancer."

Now that we can see the epigenetic landscape in three dimensions,
we are open to even more opportunities and challenges. The discovery
of point mutations in human disease
long preceded our ability to selectively drug them. Nevertheless, we
are at the cusp of being able to target
chromatin structure therapeutically.
Several presentations in the Thalassemia and Globin Gene Regulation
oral sessions today at 9:30 a.m. will
describe therapeutic manipulation
of the gamma-globin locus, while
another uses CRISPR gene-editing
techniques. Whether future therapies rely on genome editing or on
specific targeting of structural modifiers, the potential applications are
staggering. Put on your 3-D glasses
and strap in.
Dr. Blachly indicated no relevant
conflicts of interest.

Attendees listen to a Product Theater presentation Saturday.

Search through this section for today's scavenger hunt clues.
Post your photos to Twitter or Instagram using the hashtag #ASHunt16



Table of Contents for the Digital Edition of ASH News Daily 2016 - Issue 2

ASH News Daily 2016 - Issue 2 - A-1
ASH News Daily 2016 - Issue 2 - A-2
ASH News Daily 2016 - Issue 2 - A-3
ASH News Daily 2016 - Issue 2 - A-4
ASH News Daily 2016 - Issue 2 - A-5
ASH News Daily 2016 - Issue 2 - A-6
ASH News Daily 2016 - Issue 2 - A-7
ASH News Daily 2016 - Issue 2 - A-8
ASH News Daily 2016 - Issue 2 - A-9
ASH News Daily 2016 - Issue 2 - A-10
ASH News Daily 2016 - Issue 2 - A-11
ASH News Daily 2016 - Issue 2 - A-12
ASH News Daily 2016 - Issue 2 - A-13
ASH News Daily 2016 - Issue 2 - A-14
ASH News Daily 2016 - Issue 2 - A-15
ASH News Daily 2016 - Issue 2 - A-16
ASH News Daily 2016 - Issue 2 - A-17
ASH News Daily 2016 - Issue 2 - A-18
ASH News Daily 2016 - Issue 2 - A-19
ASH News Daily 2016 - Issue 2 - A-20
ASH News Daily 2016 - Issue 2 - A-21
ASH News Daily 2016 - Issue 2 - A-22
ASH News Daily 2016 - Issue 2 - A-23
ASH News Daily 2016 - Issue 2 - A-24
ASH News Daily 2016 - Issue 2 - A-25
ASH News Daily 2016 - Issue 2 - A-26
ASH News Daily 2016 - Issue 2 - B-1
ASH News Daily 2016 - Issue 2 - B-2
ASH News Daily 2016 - Issue 2 - B-3
ASH News Daily 2016 - Issue 2 - B-4
ASH News Daily 2016 - Issue 2 - B-5
ASH News Daily 2016 - Issue 2 - B-6
ASH News Daily 2016 - Issue 2 - B-7
ASH News Daily 2016 - Issue 2 - B-8
ASH News Daily 2016 - Issue 2 - B-9
ASH News Daily 2016 - Issue 2 - B-10
ASH News Daily 2016 - Issue 2 - B-11
ASH News Daily 2016 - Issue 2 - B-12
ASH News Daily 2016 - Issue 2 - B-13
ASH News Daily 2016 - Issue 2 - B-14
ASH News Daily 2016 - Issue 2 - B-15
ASH News Daily 2016 - Issue 2 - B-16
ASH News Daily 2016 - Issue 2 - B-17
ASH News Daily 2016 - Issue 2 - B-18
ASH News Daily 2016 - Issue 2 - B-19
ASH News Daily 2016 - Issue 2 - B-20
ASH News Daily 2016 - Issue 2 - B-21
ASH News Daily 2016 - Issue 2 - B-22
ASH News Daily 2016 - Issue 2 - B-23
ASH News Daily 2016 - Issue 2 - B-24
ASH News Daily 2016 - Issue 2 - B-25
ASH News Daily 2016 - Issue 2 - B-26
ASH News Daily 2016 - Issue 2 - B-27
ASH News Daily 2016 - Issue 2 - B-28
ASH News Daily 2016 - Issue 2 - B-29
ASH News Daily 2016 - Issue 2 - B-30
ASH News Daily 2016 - Issue 2 - B-31
ASH News Daily 2016 - Issue 2 - B-32
ASH News Daily 2016 - Issue 2 - B-33
ASH News Daily 2016 - Issue 2 - B-34
ASH News Daily 2016 - Issue 2 - B-35
ASH News Daily 2016 - Issue 2 - B-36
ASH News Daily 2016 - Issue 2 - B-37
ASH News Daily 2016 - Issue 2 - B-38
ASH News Daily 2016 - Issue 2 - B-39
ASH News Daily 2016 - Issue 2 - B-40
ASH News Daily 2016 - Issue 2 - B-41
ASH News Daily 2016 - Issue 2 - B-42
ASH News Daily 2016 - Issue 2 - B-43
ASH News Daily 2016 - Issue 2 - B-44
ASH News Daily 2016 - Issue 2 - B-45
ASH News Daily 2016 - Issue 2 - B-46
ASH News Daily 2016 - Issue 2 - B-47
ASH News Daily 2016 - Issue 2 - B-48
ASH News Daily 2016 - Issue 2 - C-1
ASH News Daily 2016 - Issue 2 - C-2
ASH News Daily 2016 - Issue 2 - C-3
ASH News Daily 2016 - Issue 2 - C-4
ASH News Daily 2016 - Issue 2 - C-5
ASH News Daily 2016 - Issue 2 - C-6
ASH News Daily 2016 - Issue 2 - C-7
ASH News Daily 2016 - Issue 2 - C-8
ASH News Daily 2016 - Issue 2 - C-9
ASH News Daily 2016 - Issue 2 - C-10
ASH News Daily 2016 - Issue 2 - C-11
ASH News Daily 2016 - Issue 2 - C-12
ASH News Daily 2016 - Issue 2 - C-13
ASH News Daily 2016 - Issue 2 - C-14
ASH News Daily 2016 - Issue 2 - C-15
ASH News Daily 2016 - Issue 2 - C-16
ASH News Daily 2016 - Issue 2 - C-17
ASH News Daily 2016 - Issue 2 - C-18
ASH News Daily 2016 - Issue 2 - C-19
ASH News Daily 2016 - Issue 2 - C-20
ASH News Daily 2016 - Issue 2 - C-21
ASH News Daily 2016 - Issue 2 - C-22
ASH News Daily 2016 - Issue 2 - C-23
ASH News Daily 2016 - Issue 2 - C-24
ASH News Daily 2016 - Issue 2 - C-25
ASH News Daily 2016 - Issue 2 - C-26
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