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 the patients, with some children experiencing an aggressive disease course while others get better with very little treatment. 

Our research over the past decade has shown the following:

1) The presence of more than one mutation at diagnosis portends a poor outcome.  2) DNA methylation profiling can identify patients who are most likely to experience favorable outcomes with little to no therapy.  3) The MEK inhibitor trametinib was effective in a phase II clinical trial (NCT03190915)for patients with relapsed or refractory JMML. 

We have now opened a clinical trial that incorporates all of the above findings and risk-stratifies 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. This trial moves trametinib into the front-line setting in combination with azacitidine. This clinical trial is being conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium and is funded by the National Cancer Institute (R37). This trial (NCT05849662) is open and is currently enrolling patients.

Research Funding

  • August 1, 2022 - July 31, 2027 - Implementation of an interventional, risk-adapted clinical trial for children with newly diagnosed juvenile myelomonocytic leukemia. , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R37CA266550
  • January 1, 2017 - December 31, 2021 - Targeting SETBP1 in Myeloproliferative Disorders , Principal Investigator . Sponsor: NIH, 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. Johns C, Erickson C, Jacobs A, Moon J, Baggott C, Dagher R, Nadel H, Balagtas J, Aftandilian C, Ramakrishna S, Lacayo N, Davis KL, Stieglitz E, Schultz L. Case report: sub-clinical extramedullary B-ALL in the setting of relapse following targeted therapy. Front Immunol. 2024; 15:1423487.  View on PubMed
  2. Stieglitz E, Lee AG, Angus SP, Davis C, Barkauskas DA, Hall D, Kogan SC, Meyer J, Rhodes SD, Tasian SK, Xuei X, Shannon K, Loh ML, Fox E, Weigel BJ. Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group. Cancer Discov. 2024 Sep 04; 14(9):1590-1598.  View on PubMed
  3. Zheng H, Zhao P, Tan Z, Yu WM, Werner J, Stieglitz E, Porter C, Chandrakasan S, Wechsler D, Mendez-Ferrer S, Qu CK. Prototypical innate immune mechanism hijacked by leukemia-initiating mutant stem cells for selective advantage and immune evasion in Ptpn11-associated juvenile myelomonocytic leukemia. Res Sq. 2024 Aug 02.  View on PubMed
  4. Wintering A, Hecht A, Meyer J, Wong EB, Hübner J, Abelson S, Feldman K, Kennedy VE, Peretz CAC, French DL, Maguire JA, Jobaliya C, Vasquez MR, Desai S, Dulman R, Nemecek E, Haines H, Hammad M, El Haddad A, Kogan SC, Abdullaev Z, Chehab FF, Tasian SK, Smith CC, Loh ML, Stieglitz E. LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia. Haematologica. 2024 08 01; 109(8):2533-2541.  View on PubMed
  5. Kasap C, Izgutdina A, Patiño-Escobar B, Kang A, Chilakapati N, Akagi N, Johnson H, Rashid T, Werner J, Barpanda A, Geng H, Lin YT, Rampersaud S, Gil-Alós D, Sobh A, Dupéré-Richer D, Wicaksono G, Kawehi Kelii KM, Dalal R, Ramos E, Vijayanarayanan A, Salangsang F, Phojanakong P, Serrano JAC, Zakraoui O, Tariq I, Steri V, Shanmugam M, Boise LH, Kortemme T, Stieglitz E, Licht JD, Karlon WJ, Barwick BG, Wiita AP. Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells. bioRxiv. 2024 Feb 28.  View on PubMed
  6. Elliot Stieglitz, Lauren Pommert. Risk-stratified Treatment for Pediatric Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia. The Hematologist. 2024 Feb 21; 21(2).  View on PubMed
  7. Feldman K, Aaronson K, Gu T, Ige K, Southworth E, Sanchez L, Stieglitz E. Desensitization using pegaspargase in the era of commercially available Erwinia: A single-institution report on efficacy, cost, and resource utilization. Pediatr Blood Cancer. 2024 Apr; 71(4):e30891.  View on PubMed
  8. William C. Temple, Adila Izgutdina, Matthew A. Nix, Benjamin J. Huang, Paul Phojanakong, Juan Antonio Camara Serrano, Fernando Salangsang, Veronica Steri, Simayijiang Xirenayi, Elliot Stieglitz, Arun P. Wiita. Preclinical Development and Characterization of Humanized Anti-CD72 Nanobody Chimeric Antigen Receptor T Cells for B Cell Malignancies. Transplantation and Cellular Therapy. 2024 Feb 1; 30(2):s174-s175.  View on PubMed
  9. Verma A, Chi YY, Malvar J, Lamble A, Chaudhury S, Agarwal A, Li HT, Liang G, Leong R, Brown PA, Kaplan J, Schafer ES, Slone T, Pauly M, Chang BH, Stieglitz E, Wayne AS, Hijiya N, Bhojwani D. Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium. Cancers (Basel). 2024 Jan 24; 16(3).  View on PubMed
  10. Satty A, Stieglitz E, Kucine N. Too many white cells-TAM, JMML, or something else? Hematology Am Soc Hematol Educ Program. 2023 Dec 08; 2023(1):37-42.  View on PubMed
  11. Elliot Stieglitz, Alex Lee, Steven P. Angus, Christopher Davis, Donald Barkauskas, David Hall, Scott C. Kogan, Julia Meyer, Steven D. Rhodes, Xiaoling Xuei, Kevin Shannon, Mignon L. Loh, Elizabeth Fox, Brenda J. Weigel. Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: A Report from the Children's Oncology Group. Blood. 2023 Nov 28; 142(Supplement 1):74.  View on PubMed
  12. Timothy T. Ferng, Samantha M. Pintar, Vanessa E. Kennedy, Theodore C. Tarver, Shaheen Kabir, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Juwita Hübner, Carolina E. Morales, Jose M. Rivera, Aaron C. Logan, Benjamin Braun, Elliot Stieglitz, Luke A. Gilbert, Catherine C. Smith. Mediator Kinase/CDK8 Inhibition As a Strategy to Improve FLT3 Inhibitor Activity in Acute Myeloid Leukemia. Blood. 2023 Nov 28; 142(Supplement 1):4173.  View on PubMed
  13. Bogdan Popescu, Elliot Stieglitz, Catherine C. Smith. RAS MULTI(ON) Inhibitor RMC-7977 Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 Inhibitors in AML Models. Blood. 2023 Nov 28; 142(Supplement 1):2793.  View on PubMed
  14. Elliot Stieglitz, Yueh-Yun Chi, Bill H. Chang, Sarah K. Tasian, Marielle Yohe, Christopher C Dvorak, Erica Southworth, Janel R. Long-Boyle, Jessica Van Ziffle, Zied Abdullaev, Roy Leong, Alan S. Wayne, Deepa Bhojwani, Mignon L. Loh. Risk Stratified Treatment for Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia: A Phase 1/2 Non-Randomized Study of Trametinib and Azacitidine with or without Chemotherapy. Blood. 2023 Nov 28; 142(Supplement 1):3210.  View on PubMed
  15. Cheryl A C Peretz, Elaine Tran, Bogdan Popescu, Vanessa E. Kennedy, Tanya Kumar, Lisa McGary, Natalie Tantisira, Eric Wong, Jose M. Rivera, Simayijiang Xirenayi, Elliot Stieglitz, Catherine C. Smith, Juwita Hübner. Threshold Attenuation of Perk Signaling Is Sufficient to Overcome RAS-Mediated FLT3 Inhibitor Resistance. Blood. 2023 Nov 28; 142(Supplement 1):4171.  View on PubMed
  16. Temple WC, Nix MA, Naik A, Izgutdina A, Huang BJ, Wicaksono G, Phojanakong P, Serrano JAC, Young EP, Ramos E, Salangsang F, Steri V, Xirenayi S, Hermiston M, Logan AC, Stieglitz E, Wiita AP. Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies. J Immunother Cancer. 2023 11 24; 11(11).  View on PubMed
  17. Popescu B, Stahlhut C, Tarver TC, Wishner S, Lee BJ, Peretz CAC, Luck C, Phojanakong P, Camara Serrano JA, Hongo H, Rivera JM, Xirenayi S, Chukinas JA, Steri V, Tasian SK, Stieglitz E, Smith CC. Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML. Cell Rep Med. 2023 11 21; 4(11):101290.  View on PubMed
  18. Pierpont EI, Bennett AM, Schoyer L, Stronach B, Anschutz A, Borrie SC, Briggs B, Burkitt-Wright E, Castel P, Cirstea IC, Draaisma F, Ellis M, Fear VS, Frone MN, Flex E, Gelb BD, Green T, Gripp KW, Khoshkhoo S, Kieran MW, Kleemann K, Klein-Tasman BP, Kontaridis MI, Kruszka P, Leoni C, Liu CZ, Merchant N, Magoulas PL, Moertel C, Prada CE, Rauen KA, Roelofs R, Rossignol R, Sevilla C, Sevilla G, Sheedy R, Stieglitz E, Sun D, Tiemens D, White F, Wingbermühle E, Wolf C, Zenker M, Andelfinger G. The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy. Am J Med Genet A. 2024 04; 194(4):e63477.  View on PubMed
  19. Shumock SS, Temple WC, Marinoff A, Aaronson K, Southworth E, Xirenayi S, Lee AG, Leung SG, Sweet-Cordero EA, Hermiston M, Higham C, Stieglitz E. Pre-and post-HSCT use of TKI therapy for fusion-driven B-ALL: A case series of five pediatric, adolescent and young adult patients. Cancer Rep (Hoboken). 2023 12; 6(12):e1901.  View on PubMed
  20. Mandal K, Wicaksono G, Yu C, Adams JJ, Hoopmann MR, Temple WC, Izgutdina A, Escobar BP, Gorelik M, Ihling CH, Nix MA, Naik A, Xie WH, Hübner J, Rollins LA, Reid SM, Ramos E, Kasap C, Steri V, Serrano JAC, Salangsang F, Phojanakong P, McMillan M, Gavallos V, Leavitt AD, Logan AC, Rooney CM, Eyquem J, Sinz A, Huang BJ, Stieglitz E, Smith CC, Moritz RL, Sidhu SS, Huang L, Wiita AP. Structural surfaceomics reveals an AML-specific conformation of integrin β2 as a CAR T cellular therapy target. Nat Cancer. 2023 Nov; 4(11):1592-1609.  View on PubMed

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