ASH News Daily 2017 - Issue 4 - A-2

ASH News Daily

Page A-2

Tuesday, December 12, 2017

®

ASH News Daily
2017 Editorial Board
Editor

Saad Zafar
Usmani, MD,
FACP,
Levine Cancer
Institute,
Charlotte, NC
@szusmani
Authors

Farrukh
Awan, MD,
The Ohio
State
University,
Columbus,
OH
@awandoc
Mehdi
Hamadani,
MD, Medical
College of
Wisconsin,
Milwaukee, WI
@medihumandani
Lynne
Lederman,
PhD,
Mamaroneck,
NY
@lynnelederman

CLL

Big Strides on Display for CLL
By Farrukh awan, Md

T

he area of chronic lymphocytic leukemia (CLL) has
undergone tremendous advancement in the last few years,
as reflected by multiple new therapeutic approaches that have significantly improved patient outcomes
as well as our understanding of the
disease processes. Continuing this
trend, this year's annual meeting
was remarkable for CLL and provided the opportunity to witness
some sensational findings. Here are
a few highlights:
The oral session (abstract #54) on
disease biology and pathophysiology provided a detailed analysis
of next-generation sequencing for
IGHV-D-J mutations in CD5+ B
cells and reported on accumulating
clonal complexity and expansion as
predictors of time to first treatment.
This was followed by exciting data
from numerous studies on the CLL

methylome. Notable among those
was abstract #55, which described
single-cell DNA methylome analyses characterizing epimutations as
a function of transcriptional distances between individual cancer
cells, and providing insight into the
epigenetics of CLL evolution. These
methylation signatures can be used
as predictive tools as shown in the
analysis of the LRF CLL4, ARCTIC,
and ADMIRE trials in abstract #56.
T cell exhaustion is well described in patients with CLL. From
the poster session on Saturday,
abstract #1713 detailed the development of T cell exhaustion as a
function of progressive disease,
possibly driven by the B cell clone
or by IL-10 receptor deficiency
(abstract #385). These exhausted
T cells with increased expression
of PD1 were also shown to be enriched in the lymph nodes rather
than the peripheral blood compartment (abstract #4281). This, along

with increased numbers and activity of myeloid-derived suppressor
cells (abstract #4294) and an immunosuppressive phenotype promotes the progression of the CLL
clone, and hence could be targeted
with immune-modulating agents.
Along the same lines, abstract
#1728 also described the role CLLderived exosomes play in redirecting CD14+ monocytes to promote
bone marrow fibrosis and inhibit
myeloid progenitor proliferation.
These effects, however, can be possibly overcome by some of the novel kinase inhibitors, as previously
reported with ibrutinib and now
also with acalabrutinib in abstract
#1741. Another interesting development was the data surrounding
the ability to generate and identify
antigen-specific T cells in abstract
#386, and their ability to target leukemic cells, which as the authors of

cation session "Myeloproliferative
Neoplasms: New Insights in the
Current Treatment Paradigm," held
on both Sunday and Monday. Drs.
Green, Alessandro Vannucchi, and
Claire Harrison reviewed increasingly personalized therapeutic approaches and discussed the current
status of research on the biology
of these conditions, and how new
insights have informed our understanding of disease behavior.
Dr. Green began the program
with a talk focusing on the evolution
of MPNs from their pathogenic origins through emergence of disease
to clinical progression. This process
centers on the development of one of
the cardinal and mutually exclusive

mutations in JAK2, CALR, or MPL.
These mutations serve as drivers of
the myeloproliferative phenotype
and converge on activation of JAKSTAT signaling. While these drivers
are necessary for the development of
an MPN they are generally not sufficient, with acquisition of additional
driver mutations and co-existent
host factors required for clonal outgrowth and disease manifestation.
This evolutionary pathway differs
between patients and leads to some
of the phenotypic diversity of these
conditions. Dr. Green reviewed the
complex impact that several other
genetic elements including germline
predisposition, additional somatic
mutations, and the order of mutation acquisition can have on the disease presentation, behavior, and risk
of progression. He also demonstrated a new, comprehensive genomic
tool that has been developed to provide a detailed, personalized prediction for patients dealing with these
disorders.
Next, Dr. Vannucchi provided
a more thorough review of the
clinical environment around polycythemia vera (PV) and essential thrombocytosis (ET). Despite
steps toward a more consistent,
biologically based characterization
of these diseases, significant heterogeneity persists in terms of real
world diagnostic test utilization
and treatment application. Important updates from the revised 2016

»» CLL Page A-6

MPNs

Oh myeLoid
By Peter ForSBerg, Md, and
nina Shah, Md

Hugh Young
Rienhoff, MD,
MyDaughters
DNA.org,
Imago
BioSciences,
San Carlos, CA
Nina Shah,
MD,
University
of California,
San Francisco,
CA
@ninashah33

T

he myeloproliferative neoplasm (MPN) landscape has
seen tremendous advancements since the seminal description of the JAK2 V617F mutation
in 2005. As Dr. Antony Green describes, "This is an exciting time for
the MPN field. Molecular insights
in the last 12 years have revolutionized the way we diagnose patients,
have led to new therapeutic approaches, and have laid the foundation for the provision of patientspecific personalized predictions."
These dynamic improvements
were front and center at the edu-

Binod Dhakal, MD, MS, Medical College of Wisconsin; and
Peter Forsberg, MD, University of Colorado, are serving
as a Junior Authors this year.
©2017 by the American Society of
Hematology
All materials contained in this
newspaper are protected by
copyright laws and may not be
used, reproduced, or otherwise
exploited in any manner without
the expressed prior permission of
ASH News Daily.
Contributing authors have declared
any financial interest in a product
or in potentially competing
products, regardless of the dollar
amount. Any such financial interest
is noted with the respective articles.

Dr. Yulia Lin speaks during the ASH "Choosing Wisely Campaign: 2017
ASH Choosing Wisely Champions" session on Monday.

»» MYELOID Page A-6



http://www.DNA.org

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 4

ASH News Daily 2017 - Issue 4 - A-1
ASH News Daily 2017 - Issue 4 - A-2
ASH News Daily 2017 - Issue 4 - A-3
ASH News Daily 2017 - Issue 4 - A-4
ASH News Daily 2017 - Issue 4 - A-5
ASH News Daily 2017 - Issue 4 - A-6
ASH News Daily 2017 - Issue 4 - A-7
ASH News Daily 2017 - Issue 4 - A-8
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