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Calendar
2019 American Society of Clinical
Oncology Annual Meeting
European Hematology Association
Annual Congress
May 31 – June 4, 2019
Chicago, IL
The American Society of Clinical Oncology brings
together 32,000 oncology professionals from around
the world to discuss state-of-the-art treatment
modalities, new therapies, and ongoing controversies
in the field.
Athens, Greece
Highlights of ASH® in the
Mediterranean
March 15 – 16, 2019
Athens, Greece
Highlights of ASH® in Latin America
April 5 – 6, 2019
Lima, Peru
June 13 – 16, 2019
Amsterdam, The Netherlands
The 24th Annual Congress covers every subspecialty in
hematology, with experts from around the world sharing
original data and discussing the latest evidence-based
approaches to treating hematologic disorders.
2019 American Association for
Cancer Research Annual Meeting
March 29 – April 3, 2019
Atlanta, GA
The annual meeting will explore the topics of
integrative cancer science, global impact, and
individualized patient care by bringing together
researchers and clinicians from international
institutions.
Oncology Nursing Society
Annual Congress
April 11 – 14, 2019
Anaheim, CA
The 44th Annual Congress features the latest
in research, clinical practice, advanced practice,
and leadership, presented by oncology nursing
professionals.
2nd AMP Global 2019 Congress on
Molecular Pathology
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
May 16 – 18, 2019
Hong Kong, China
The Association for Molecular Pathology’s second
congress brings together a multidisciplinary net-
work of molecular and diagnostics professionals to
discuss its applications in health care.
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
4th International Symposium on
Immunotherapy
May 24 – 25, 2019
London, UK
The Institute for Cancer Vaccines and Immunother-
apy’s symposium will feature discussions about
the impact of immunotherapies like checkpoint
inhibitors and chimeric antigen receptor T-cell
therapies in a variety of tumor types.
June 18 – 22, 2019
Lugano, Switzerland
At the 15th International Conference on Malignant
Lymphoma, the scientific community involved in the
study and treatment of lymphoid neoplasms present
the latest basic and translational science in the field.
CDK9 regulation of MCL-1
inhibits apoptosis, enabling
National Comprehensive Cancer
Network 24th Annual Conference
March 21 – 23, 2019
Orlando, FL
With the theme of “Improving the Quality,
Effectiveness, and Efficiency of Cancer Care,”
the annual conference brings together oncology
professionals to discuss the data upon which the
NCCN Guidelines® are based.
International Conference on Malignant
Lymphoma
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
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