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 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 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