Research Summary

Juvenile myelomonocytic leukemia (JMML) is a blood cancer that affects young children and is often difficult to diagnose and treat. Currently available therapies cure only half of patients, with some children experiencing an aggressive disease course while a rare group get better with very little treatment. We have now shown that presence of secondary mutations at diagnosis predicts a poor outcome. We have also shown that DNA methylation profiling can identify patients most likely to experience favorable outcomes.

We are currently running a clinical trial through the Children's Oncology Group for patients with relapsed and refractory JMML. This trial is testing the safety and efficacy of the oral MEK inhibitor, trametinib. This trial is based on extensive pre-clinical testing and a strong genomic rationale. This trial marks an important step towards more effectively treating patients with Ras driven leukemia using targeted agents.

Our next trial will risk-stratify patients with newly diagnosed JMML to receive different therapies tailored to the risk of relapse predicted by both the number of mutations and DNA methylation signatures at diagnosis.

Research Funding

  • January 1, 2017 - December 31, 2021 - Targeting SETBP1 in Myeloproliferative Disorders, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: K08HL135434
  • January 1, 2017 - December 31, 2021 - Targeting SETBP1 in Myeloproliferative Disorders, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: K08HL135434
  • January 1, 2017 - December 31, 2021 - Targeting SETBP1 in Myeloproliferative Disorders, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: K08HL135434
  • January 1, 2017 - December 31, 2021 - Targeting SETBP1 in Myeloproliferative Disorders, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: K08HL135434

Education

Yeshiva University, New York, B.A., 06/03, Biology
Stony Brook School of Medicine, New York, M.D., 06/08, Medicine
NYPH - Weill Cornell Medical Center, New York, Residency, 06/11, Pediatrics
University of California, San Francisco, Fellowship, 07/14, Pediatric Heme/Onc

Honors & Awards

  • 2008
    Barry S. Coller International Research Award, Stony Brook University
  • 2008
    Global Public Health Intern, Naval Medical Research Center, Peru
  • 2012-2013
    Trainee on NIH T32 Grant, “Research Training in Childhood Cancer”
  • 2013
    AACR “Molecular Biology in Clinical Oncology” workshop, Aspen, CO
  • 2014-2016
    St. Baldrick’s Foundation Fellowship Award
  • 2014
    ASH Annual Meeting Abstract Achievement Award, San Francisco, CA
  • 2014
    JMML Symposium Abstract Award San Francisco, CA
  • 2015-2017
    NIH Extramural Loan Repayment Program Award for Pediatric Research
  • 2015-2017
    Alex’s Lemonade Stand Foundation, Young Investigator Award
  • 2015
    Northwestern Mutual Foundation Research Award
  • 2015
    SIOP Young Investigator Award, Cape Town, South Africa
  • 2016
    ASH/EHA Translational Training in Hematology Program, Milan/Copenhagen/San Diego
  • 2016
    American Cancer Society , Individual Research Award
  • 2016-2018
    Rally Foundation for Childhood Cancer, Research Award
  • 2017-2021
    NIH K08 Award, National Heart Lung Blood Institute

Selected Publications

  1. Kennedy AL, Myers KC, Bowman J, Gibson CJ, Camarda ND, Furutani E, Muscato GM, Klein RH, Ballotti K, Liu S, Harris CE, Galvin A, Malsch M, Dale D, Gansner JM, Nakano TA, Bertuch A, Vlachos A, Lipton JM, Castillo P, Connelly J, Churpek J, Edwards JR, Hijiya N, Ho RH, Hofmann I, Huang JN, Keel S, Lamble A, Lau BW, Norkin M, Stieglitz E, Stock W, Walkovich K, Boettcher S, Brendel C, Fleming MD, Davies SM, Weller EA, Bahl C, Carter SL, Shimamura A, Lindsley RC Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.  View on PubMed
  2. Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-risk Leukemias: A Report from the LEAP Consortium.  View on PubMed
  3. Pikman Y, Stieglitz E Targeting the Ras pathway in pediatric hematologic malignancies.  View on PubMed
  4. Hecht A, Meyer JA, Behnert A, Wong E, Chehab F, Olshen A, Hechmer A, Aftandilian C, Bhat R, Choi SW, Chonat S, Farrar JE, Fluchel M, Frangoul H, Han JH, Kolb EA, Kuo DJ, MacMillan ML, Maese L, Maloney KW, Narendran A, Oshrine B, Schultz KR, Sulis ML, Van Mater D, Tasian SK, Hofmann WK, Loh ML, Stieglitz E Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.  View on PubMed
  5. Alyssa L. Kennedy, Kasiani C. Myers, James Bowman, Christopher J. Gibson, Gwen M. Muscato, Robert Klein, Kaitlyn Ballotti, Nicholas Camarda, Elissa M. Furutani, Chad E. Harris, Shanshan Liu, Ashley Galvin, Maggie Malsch, David C. Dale, John M Gansner, Taizo A. Nakano, Alison A. Bertuch, Adrianna Vlachos, Jeff H. Lipton, Paul Castillo, James Connelly, John Edwards, Nobuko Hijiya, Richard Ho, Inga Hofmann, James N Huang, Sioban B. Keel, Adam J. Lamble, Bonnie W Lau, Kelly J. Walkovich, Maxim Norkin, Wendy Stock, Steffen Boettcher, Christian Brendel, Elliot Stieglitz, Mark D. Fleming, Stella M. Davies, Edie A. Weller, Chris Bahl, Scott L. Carter, Akiko Shimamura, R. Coleman Lindsley Distinct Genetic Pathways Define Leukemia Predisposition Versus Adaptive Clonal Hematopoiesis in Shwachman-Diamond Syndrome.  View on PubMed
  6. Astrid Behnert, Julia Meyer, Jahan-Yar Parsa, Aaron Hechmer, Mignon L. Loh, Adam B. Olshen, Adam J. de Smith, Elliot Stieglitz Genetic Alterations Precede DNA Methylation Changes in Juvenile Myelomonocytic Leukemia.  View on PubMed
  7. Levinson A, Lee AG, Martell HJ, Breese MR, Zaloudek C, Van Ziffle J, Laguna B, Leung SG, Chen MD, Chen LM, Pfeil J, Ladwig NR, Shah AT, Behroozfard I, Rao AA, Salama SR, Sweet-Cordero EA, Stieglitz E Complete Response to PD-1 Inhibition in an Adolescent With Relapsed Clear Cell Adenocarcinoma of the Cervix Predicted by Neoepitope Burden and APOBEC Signature.  View on PubMed
  8. Schönung M, Meyer J, Nöllke P, Olshen AB, Hartmann M, Murakami N, Wakamatsu M, Okuno Y, Plass C, Loh ML, Niemeyer CM, Muramatsu H, Flotho C, Stieglitz E, Lipka DB International Consensus Definition of DNA Methylation Subgroups in Juvenile Myelomonocytic Leukemia.  View on PubMed
  9. Contreras CF, Higham CS, Behnert A, Kim K, Stieglitz E, Tasian SK Clinical utilization of blinatumomab and inotuzumab immunotherapy in children with relapsed or refractory B-acute lymphoblastic leukemia.  View on PubMed
  10. Behnert A, Lee AG, Young EP, Breese MR, Leung SG, Behroozfard I, Maruffi M, Sweet-Cordero EA, Dvorak CC, Chu J, Stieglitz E NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML.  View on PubMed
  11. Fabrizio VA, Kernan NA, Boulad F, Cancio M, Allen J, Higman M, Margossian SP, Mauguen A, Prockop S, Scaradavou A, Shah N, Spitzer B, Stieglitz E, Yeager N, O'Reilly RJ, Brentjens RJ, Jan Boelens J, Curran KJ Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant.  View on PubMed
  12. Dueck ME, Lin R, Zayac A, Gallagher S, Chao AK, Jiang L, Datwani SS, Hung P, Stieglitz E Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform.  View on PubMed
  13. Friend BD, Bailey-Olson M, Melton A, Shimano KA, Kharbanda S, Higham C, Winestone LE, Huang J, Stieglitz E, Dvorak CC The impact of total body irradiation-based regimens on outcomes in children and young adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.  View on PubMed
  14. Julia Meyer, Maximillian Schönung, Christian Flotho, Adam B. Olshen, Mark Hartmann, Christoph Plass, Yusuke Okuno, Yoshiyuki Takahashi, Norihiro Murakami, Manabu Wakamatsu, Mignon L. Loh, Charlotte M. Niemeyer, Hideki Muramatsu, Daniel B. Lipka, Elliot Stieglitz DNA Methylation As a Biomarker of Outcome in JMML: An International Effort Towards Clinical Implementation.  View on PubMed
  15. Matthew Nix, Yu-Hsiu T. Lin, Huimin Geng, Makeba Marcoulis, Paul Phojanakong, Donghui Wang, Veronica Steri, Jeffrey Whitman, Sagar Bapat, Elliot Stieglitz, Anne Deucher, Kristie L White, Byron C Hann, Arun P. Wiita In Vitro-Selected Nanobody-Based Cellular Therapy Targeting CD72 for Treatment of Refractory B-Cell Malignancies.  View on PubMed
  16. Chao AK, Meyer JA, Lee AG, Hecht A, Tarver T, Van Ziffle J, Koegel AK, Golden C, Braun BS, Sweet-Cordero EA, Smith CC, Dvorak CC, Loh ML, Stieglitz E Fusion driven JMML: a novel CCDC88C-FLT3 fusion responsive to sorafenib identified by RNA sequencing.  View on PubMed
  17. Hecht A, Meyer J, Chehab FF, White KL, Magruder K, Dvorak CC, Loh ML, Stieglitz E Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia.  View on PubMed
  18. de Smith AJ, Lavoie G, Walsh KM, Aujla S, Evans E, Hansen HM, Smirnov I, Kang AY, Zenker M, Ceremsak JJ, Stieglitz E, Muskens IS, Roberts W, McKean-Cowdin R, Metayer C, Roux PP, Wiemels JL Predisposing germline mutations in high hyperdiploid acute lymphoblastic leukemia in children.  View on PubMed
  19. Capri Y, Flex E, Krumbach OHF, Carpentieri G, Cecchetti S, Lißewski C, Rezaei Adariani S, Schanze D, Brinkmann J, Piard J, Pantaleoni F, Lepri FR, Goh ES, Chong K, Stieglitz E, Meyer J, Kuechler A, Bramswig NC, Sacharow S, Strullu M, Vial Y, Vignal C, Kensah G, Cuturilo G, Kazemein Jasemi NS, Dvorsky R, Monaghan KG, Vincent LM, Cavé H, Verloes A, Ahmadian MR, Tartaglia M, Zenker M Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome.  View on PubMed
  20. Iacobucci I, Wen J, Meggendorfer M, Choi JK, Shi L, Pounds SB, Carmichael CL, Masih KE, Morris SM, Lindsley RC, Janke LJ, Alexander TB, Song G, Qu C, Li Y, Payne-Turner D, Tomizawa D, Kiyokawa N, Valentine M, Valentine V, Basso G, Locatelli F, Enemark EJ, Kham SKY, Yeoh AEJ, Ma X, Zhou X, Sioson E, Rusch M, Ries RE, Stieglitz E, Hunger SP, Wei AH, To LB, Lewis ID, D'Andrea RJ, Kile BT, Brown AL, Scott HS, Hahn CN, Marlton P, Pei D, Cheng C, Loh ML, Ebert BL, Meshinchi S, Haferlach T, Mullighan CG Genomic subtyping and therapeutic targeting of acute erythroleukemia.  View on PubMed

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