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. Meyer JA, Xirenayi S, Werner J, Turakulov R, Hechmer A, Abdullaev Z, Hamdy N, Olshen A, Stieglitz E, Hammad M, Elhaddad A Clinical and molecular characterization of patients with juvenile myelomonocytic leukaemia.  View on PubMed
  2. Zheng H, Zhao P, Tan Z, Yu WM, Werner J, Stieglitz E, Porter CC, Chandrakasan S, Wechsler DS, Mendez-Ferrer S, Qu CK Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.  View on PubMed
  3. Popescu B, Jones MF, Piao M, Tran E, Koh A, Lomeli I, Peretz CAC, Murad N, Abelson S, Morales C, Rivera JM, Pikman Y, Cheng ML, Logan AC, Stieglitz E, Smith CC Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia.  View on PubMed
  4. Leardini D, Flex E, Stieglitz E, Cerasi S, Bertuccio SN, Baccelli F, Kállay K, Kjollerstrom P, Batalha S, Carpentieri G, Pedace L, Ciolfi A, Hammad M, Miranda M, Rojas M, Rao A, Innes AJ, Rudelius M, Santini V, Raddi M, Teh KH, De Vito R, Yoshimi A, Tartaglia M, Locatelli F, Niemeyer CM, Masetti R Biallelic SH2B3 germline variants are associated with a neonatal myeloproliferative disease and multisystemic involvement.  View on PubMed
  5. Shannalee Martinez, Vladimir V. Senyukov, Suheyla Hasgur, Arianexys Aquino-Lopez, Peter D. Emanuel, Yunying Lucy Liu, Elliot Stieglitz, Gregory Behbehani, Amanda R. Campbell, Dean A. Lee Juvenile myelomonocytic leukemia stem cells are sensitive to NK cell-mediated lysis and express targetable antigens.  View on PubMed
  6. Kasap C, Izgutdina A, Patiño-Escobar B, Kang AS, Chilakapati N, Akagi N, Manoj AM, Johnson H, Rashid T, Werner J, Barpanda A, Geng H, Lin YT, Rampersaud S, Gil-Alós D, Sobh A, Dupéré-Richer D, Aleman A, Wicaksono G, Kelii KMK, Dalal R, Ramos E, Vijayanarayanan A, Lakhani K, Salangsang F, Phojanakong P, Camara Serrano JA, Zakraoui O, Tariq I, Chari A, Chung A, Kumar AD, Martin T, Wolf JL, Wong S, Steri V, Shanmugam M, Boise LH, Kortemme T, Parekh S, Stieglitz E, Licht JD, Karlon W, Barwick BG, Wiita A. Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells. Blood. 2025 May 13.  View on PubMed
  7. Werner J, Lee AG, Zhang C, Abelson S, Xirenayi S, Rivera J, Yousuf K, Shin H, Patiño-Escobar B, Bachl S, Mandal K, Barpanda A, Ramos E, Izgutdina A, Chaudhuri S, Temple WC, Bhatnagar S, Dardis JK, Meyer J, Morales C, Meshinchi S, Loh ML, Braun B, Tasian SK, Wiita AP, Stieglitz E. Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia. Nat Commun. 2025 Apr 23; 16(1):3804.  View on PubMed
  8. Decker M, Huang BJ, Ware T, Boone C, Tang M, Ybarra J, Ballapuram AC, Taran KA, Chen PY, Amendáriz M, Leung CJ, Harris M, Tjoa K, Hongo H, Abelson S, Rivera J, Ngo N, Herbst DM, Suciu RM, Guijas C, Sedighi K, Andalis T, Roche E, Xie B, Liu Y, Smith CC, Stieglitz E, Niphakis MJ, Cravatt BF, Shannon K. In vivo validation of the palmitoylation cycle as a therapeutic target in NRAS-mutant cancer. bioRxiv. 2025 Mar 21.  View on PubMed
  9. Westover T, Walsh MP, Abdelhamed S, Xiong E, Ma J, Song G, Thomas ME, Umeda M, Maciaszek JL, Wong JC, Wintering A, Wang L, Emanuel PD, Loh ML, Tasian SK, Stieglitz E, Schwartz JR, Shannon KM, Klco JM Genomic landscape and clonal architecture in pediatric myeloid neoplasms with chromosome 7 deletions.  View on PubMed
  10. Grenier JM, Tasian SK, Stieglitz E, Abdullaev Z, Wertheim GB, Li MM, Phillips CA. Azacytidine Monotherapy in an Infant With Mosaic NRAS-Driven Juvenile Myelomonocytic Leukemia. Pediatr Blood Cancer. 2025 May; 72(5):e31647.  View on PubMed
  11. Marinoff AE, Thrall A, Aaronson K, Braun BS, Castellanos M, Chu J, Hermiston M, Huang BJ, Levinson A, Southworth E, Winger BA, Olshen A, Stieglitz E. Thrombopoietin Receptor Agonists for Thrombocytopenia in Pediatric Hematologic Malignancies. Pediatr Blood Cancer. 2025 Mar; 72(3):e31528.  View on PubMed
  12. Timothy T. Ferng, Samantha M. Pintar, Vanessa E. Kennedy, Shaheen Kabir, Theodore C. Tarver, Veronica Steri, Paul Phojanakong, Juwita Hübner, Carolina E. Morales, Jose M. Rivera, Aaron C. Logan, Benjamin Braun, Elliot Stieglitz, Luke A. Gilbert, Catherine C. Smith. CDK8 Inhibition Represses Monocyte-like Gene Expression in Acute Myeloid Leukemia Cells and Antagonizes In Vivo Resistance to FLT3 Inhibition. Blood. 2024 Nov 5; 144(Supplement 1):723-723.  View on PubMed
  13. Jeremy Grenier, Sarah K. Tasian, Elliot Stieglitz, Zied Abdullaev, Gerald Wertheim, Marilyn M. Li, Charles A Phillips. Effective Azacytidine Monotherapy in an Infant with Mosaic NRAS-Driven JMML. Blood. 2024 Nov 5; 144(Supplement 1):6739-6739.  View on PubMed
  14. Hiroyuki Takamatsu, Emilio Ramos, Bonell Patino-Escobar, Corynn Kasap, Adila Izgutdina, Juwita Werner, Akihito Inagaki, Takeshi Yoroidaka, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, Veronica Steri, Elliot Stieglitz, Masaki Nagato, Satoshi Tatsuno, Arun P Wiita. HLA-Pan-DP CAR-T Demonstrates Cytotoxicity Against Multiple Hematological Malignancies. Blood. 2024 Nov 5; 144(Supplement 1):1038-1038.  View on PubMed
  15. Matthew Decker, Benjamin J Huang, Tim Ware, Christopher Boone, Michelle Tang, Aishwarya Ballapuram, Julia Ybarra, Katrine Taran, Marcos Amendáriz, Camille Leung, Max Harris, Elliot Stieglitz, Micah Niphakis, Benjamin Cravatt, Kevin Shannon. In Vivo and In Vitro Chemical Synthetic Lethality of ABHD17 and MEK Inhibition in NRAS -Mutant Acute Myeloid Leukemia. Blood. 2024 Nov 5; 144(Supplement 1):5808-5808.  View on PubMed
  16. Bogdan Popescu, Madison Piao, Sydney Abelson, Carolina E. Morales, Khadija Yousuf, Jose M. Rivera, Cheryl A C Peretz, Elliot Stieglitz, Catherine C. Smith. Preclinical Activity of RAS(ON) Multi-Selective Inhibitor RMC-7977 and Therapeutic Combinations in AML with Signaling Mutations. Blood. 2024 Nov 5; 144(Supplement 1):2770-2770.  View on PubMed
  17. 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
  18. 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
  19. 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
  20. 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

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