ASH Clinical News ACN_5.1_Digital | Page 37

FEATURE
that he produced with highlights from
the 2017 ASH Annual Meeting. “This
video was seen by more than 4,000 in-
dividuals,” he said. “Indeed, I rarely see
a patient who doesn’t say, ‘I saw your
videos, and that’s part of the reason
why I came to see you – you seemed
like you cared about my disease.”
Dr. Chan agreed, noting that “as
more people get into this game, I think
we’re going to see a call to arms to not
only adjust the quality of it, but also to
start rewarding it,” just as people would
be rewarded for successful publishing
or funding track records.
This is a relatively new idea, but one
that is being explored among gradu-
ate medical education researchers. For
example, researchers from the Mayo
Clinic in Rochester recently published
a “social media promotion grading
scale,” which provides definitions of
high-, medium-, and low-impact con-
tent (determined by numbers of views
or downloads). 10
As more health-care providers flock
to apps and social media for learning,
teaching, and networking, Dr. Chan
said, it will be crucial to “think about
how we can engage in social media to
up our game [and] to value people who
can translate scientific knowledge and
broadly disseminate it.”
When asked about how social me-
dia has changed her practice, Dr. Yates
cited a different type of reward. “I’m
standing here because of social media,”
she said at the ASH annual meeting.
“I’m a clinician educator; I don’t do
research and I don’t run a lab,” she said,
which is how most doctors find rec-
ognition. “I’m speaking at the annual
meeting, and I never thought I would
have that opportunity in my career. I
took a chance [in joining social media],
and it has changed my career for the
better.” —By Emma Yasinski ●
REFERENCES
1. Creation Health, “New study reveals explosion of doctors on
Twitter.” Accessed December 10, 2018, from https://creation.
co/new-study-reveals-explosion-doctors-twitter/.
2. Nerminathan A, Harrison A, Phelps M, et al. Doctors’ use of
mobile devices in the clinical setting: a mixed methods study.
Int Med J. 2017;47:291-8.
3. Hussain A, Ali S, Ahmed M, Hussain S. The anti-vaccination
movement: a regression in modern medicine. Cureus.
2018;10:e2919.
4. Pricewaterhouse Coopers. Social media “likes” healthcare:
from marketing to social business. Accessed December 10,
2018, from www.pwc.com/us/en/health-industries/health-
research-institute/publications/pdf/health-care-social-
media-report.pdf.
5. Huberty J, Eckert R, Gowin K, et al. Feasibility study of online yoga
for symptom management in patients with myeloproliferative
neoplasms. Haematologica. 2017;102:e384-8.
6. Chan TM, Thoma B, Krishnan K, et al. Derivation of two critical
appraisal scores for trainees to evaluate online educational
resources: a METRIQ study. West J Emerg Med. 2016;17:574-84.
7. Chan TM, Grock A, Paddock M, et al. Examining reliability
and validity of an online score (ALiEM AIR) for rating free
open access medical education resources. Ann Emerg Med.
2016;68:729-35.
8. Ventola CL. Mobile devices and apps for health care
professionals: uses and benefits. P T. 2014;39:356-64.
9. Crane GM, Gardner JM. Pathology image-sharing on social
media: recommendations for protecting privacy while
motivating education. AMA J Ethics. 2016;18:817-25.
10. Cabrera D, Vartabedian BS, Spinner RJ, et al. More than likes
and tweets: creating social media portfolios for academic
promotion and tenure. J Grad Med Ed. 2017;9:421-5.
“As more people get into [the social
media–engagement] game, I think we’re
going to see a call to arms to not only
adjust the quality of it, but also to start
rewarding it.”
—TERESA CHAN, MD
CDK9 regulation of MCL-1
inhibits apoptosis, enabling
1-5
AML BLAST
SURVIVAL
CDK9
MCL-1 mRNA
MCL-1 dependence may
drive progression of AML
3,6
CDK9 is a key regulator of
MCL-1 function
1,2,5
Disease progression and
treatment resistance in a subset
of acute myeloid leukemia (AML)
have been associated with a key
anti-apoptotic protein, myeloid
cell leukemia 1 (MCL-1). 3,6 MCL-1
is a member of the apoptosis-
regulating BCL-2 family of proteins. 7 MCL-1 mRNA transcription in
AML blasts is regulated by cyclin-
dependent kinase 9 (CDK9), 1,2 a
protein that plays a critical role in
transcription regulation without
directly affecting cell-cycle control. 5,10
In MCL-1–dependent AML,* the
AML blasts depend primarily
on the function of MCL-1 for the
anti-apoptotic mechanism of
survival. 8,9 MCL-1 inhibits apoptosis
and sustains the survival of AML
blasts, allowing them to proliferate,
which may lead to relapse. 3 MCL-1
dependence is also associated
with resistance to agents that
otherwise have activity against
leukemic blasts. 7 CDK9-mediated transcriptional
regulation of anti-apoptotic
proteins, including MCL-1,
is critical for the survival of
MCL-1–dependent AML blasts. 5
Inhibition of CDK9 as a
rational therapeutic strategy
in MCL-1–dependent AML
1,5,7
Because MCL-1 has a short half-
life of 2-4 hours, the effects of
targeting its upstream regulators
are expected to reduce MCL-1
levels rapidly. 11 CDK9 inhibition
has been shown to block MCL-1
transcription, resulting in rapid
depletion of MCL-1 protein, which
may restore apoptosis in MCL-1–
dependent AML blasts. 1,5,7
Understanding the role of CDK9
in regulating MCL-1 may inform
therapeutic targeting strategies
in AML.
*The prevalence of MCL-1–dependent
AML is under investigation.
A matter of cell life
and cell death
Learn more at www.toleropharma.com
Tolero Pharmaceuticals, Inc. is a leading developer of novel therapeutics to inhibit
biological drivers of hematologic and oncologic diseases.
References: 1. Chen R, Keating MJ, Gandhi V, Plunkett W. Transcription inhibition by fl avopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood. 2005;106(7):2513-2519. 2. Ocana A, Pandiella A.
Targeting oncogenic vulnerabilities in triple negative breast cancer: biological bases and ongoing clinical studies. Oncotarget. 2017;8(13):22218-22234. 3. Glaser SP, Lee EF, Trounson E, et al. Anti-apoptotic Mcl-1
is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 2012;26(2):120-125. 4. Perciavalle RM, Opferman JT. Delving deeper: MCL-1’s contributions to normal and cancer
biology. Trends Cell Biol. 2013;23(1):22-29. 5. Sonawane YA, Taylor MA, Napoleon JV, Rana S, Contreras JI, Natarajan A. Cyclin dependent kinase 9 inhibitors for cancer therapy. J Med Chem. 2016;59(19):8667-
8684. 6. Xiang Z, Luo H, Payton JE, et al. Mcl1 haploinsuffi ciency protects mice from Myc-induced acute myeloid leukemia. J Clin Invest. 2010;120(6):2109-2118. 7. Thomas D, Powell JA, Vergez F, et al. Targeting
acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood. 2013;122(5):738-748. 8. Yoshimoto G, Miyamoto T, Jabbarzadeh-Tabrizi S, et al. FLT3-ITD up-regulates
MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD–specifi c STAT5 activation. Blood. 2009;114(24):5034-5043. 9. Butterworth M, Pettitt A, Varadarajan S, Cohen GM. BH3 profi ling
and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells. Br J Cancer. 2016;114(6):638-641. 10. Morales F, Giordano A. Overview of CDK9 as a target in cancer research. Cell Cycle.
2016;15(4):519-527. 11. Gores GJ, Kaufmann SH. Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumors. Genes Dev. 2012;26(4):305-311.
Tolero Pharmaceuticals is a registered trademark of Sumitomo Dainippon Pharma Co., Ltd. ©2018 Boston Biomedical, Inc. All rights reserved. PM-NPS-0008 4/2018