ASH News Daily 2016 - Issue 3 - A-2

ASH News Daily

Page A-2

Monday, December 5, 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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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.

S T E M C E L L B I O L O GY

Mitochondrial Message in a Bottle
By Aaron T. Gerds, MD, MS
Just an HSC
An island, lost at sea-o
Another lonely day
With no one here but BMSCs

uiescence is one of the things
that makes a stem cell a stem
cell, a state ensuring lifelong
tissue maintenance as well as providing protection from premature
exhaustion and toxic insults like chemotherapy. How do these stem cells
stay this calm and still as if relaxing
on a desert island?
"They are not simply 'silent' stem
cells waiting to be activated when
they are called upon. There are active processes keeping them in this
dormant state," noted abstract introducer Dr. John Dick. For example,
hematopoietic stem cells (HSC) have
high levels of reactive oxygen species (ROS) during leukocyte production, but in quiescence, ROS levels
are low. HSCs keep ROS levels low
by actively transferring them to bone
marrow stromal cells (BMSCs) via
direct cell-to-cell contact, thus maintaining quiescence.

Dr. Karin Golan

Dr. Karin Golan revealed in yesterday's Plenary Scientific Session
(abstract #5) that mitochondria
serve as a virtual message in bottle,
not sending a castaway's SOS to
the world, but rather sending ROS
from the HSCs to marrow stromal
cells. Through a series of elegant experiments transplanting mice with
GFP-labeled mitochondria, this international collaboration presented
evidence of the bidirectional transfer

of mitochondria between HSCs and
BMSCs. They went on to show that
connexin-43 gap junction expression
on hematopoietic progenitor cells,
but not on BM stromal cells, is specifically required for mitochondrial
transfer. Lastly, they showed that this
transfer is regulated by AMP-activated protein kinase (AMPK) signaling,
a crucial metabolic regulator.
»» STEM CELL Page A-24

H E M AT O P O I E S I S / L E U K E M I A

A reSMARCable Discovery
By James S. Blachly, MD

t's not every day that we turn up
a brand new inherited monogenic disease, discover its functional
basis, and model it in two different
species, all while elucidating new
key factors in normal hematopoiesis in one fell swoop. ASH delivers
again! Overall, yesterday's Plenary
Scientific Session was a great mix of
clinical, translational, and basic biology, but the second plenary abstract
presented was especially interesting,
as it embodied both clinical insights
and fundamental cellular biology all
in one.
Dr. Leonard Zon introduced plenary abstract #2, "SWI/SNF Protein SMARCD2 Orchestrates Transcriptional Networks Controlling
Hematopoiesis and Neutrophil
Granulocytes in Humans, Mice and
Zebrafish." This monumental work
was the product of collaboration
among investigators from at least 12
separate groups, at eight different
institutions, across four continents.
Indeed, Dr. Zon's introduction emphasized both the magnitude of the
work and the cooperation it took to
produce it. "It was amazing to collect
these very interesting patients with a
rare disease, with an important gene

PHOTO

Dr. Maximilian Witzel

that is defective, and then to understand it with an animal model,"
he summarized. "And it was quite
remarkable to use genetics to find
disorders of myeloid differentiation,
and then to turn up an epigenetic
regulator."
Dr. Maximilian Witzel, who received the ASH Outstanding Abstract Achievement Award in the
medical resident category, presented
on behalf of a large international
group of collaborators the exciting
story of four patients in three fami-

lies, all with a mysterious syndrome
of neutrophil dysfunction and skeletal abnormalities. Astute clinical
observations led to examination by
light and electron microscopy, and
the confirmation of identical, specific granule defects. With similar
clinical phenotypes, the kindreds
were examined together by highthroughput sequencing. Each family
had a unique alteration in the heretofore poorly characterized epigenetic
regulator SMARCD2. Importantly,
Speaking with ASH News Daily, Dr.
Witzel noted that two kindreds had
homozygous loss of function point
mutations, while another had an
internal duplication of genetic material that was initially missed until
a specific search for copy number
alterations was performed. He cautions other investigators not to miss
important findings in similar types
of studies.
Having identified SMARCD2 as
recurrently mutated in the affected
patients of these families, investigators studied the mutant protein
»» HEMATOPOIESIS Page A-23

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