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 others get better with very little treatment. We have now shown that the presence of more than one mutation at diagnosis portends a poor outcome. We have also shown that DNA methylation profiling can identify patients who are most likely to experience favorable outcomes with little to no therapy.

We recently completed a clinical trial conducted through the Children's Oncology Group for patients with relapsed and refractory JMML. This trial tested the safety and efficacy of the oral MEK inhibitor, trametinib. This trial met its primary objective with half of all patients experiencing an objective response. 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. This trial will move trametinib into the front-line setting in combination with azacitidine. This clinical trial will be conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium and is funded by the National Cancer Institute (R37).

Research Funding

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


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. Marinoff AE, Aaronson K, Agrawal AK, Braun BS, Golden C, Huang BJ, Michlitsch J, Southworth E, Thrall A, Vo KT, Stieglitz E. Venetoclax in combination with chemotherapy as treatment for pediatric advanced hematologic malignancies. Pediatr Blood Cancer. 2023 Jun; 70(6):e30335.  View on PubMed
  2. Pasupuleti SK, Chao K, Ramdas B, Kanumuri R, Palam LR, Liu S, Wan J, Annesley C, Loh ML, Stieglitz E, Burke MJ, Kapur R. Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia. Mol Ther. 2023 04 05; 31(4):986-1001.  View on PubMed
  3. de Blank PMK, Gross AM, Akshintala S, Blakeley JO, Bollag G, Cannon A, Dombi E, Fangusaro J, Gelb BD, Hargrave D, Kim A, Klesse LJ, Loh M, Martin S, Moertel C, Packer R, Payne JM, Rauen KA, Rios JJ, Robison N, Schorry EK, Shannon K, Stevenson DA, Stieglitz E, Ullrich NJ, Walsh KS, Weiss BD, Wolters PL, Yohay K, Yohe ME, Widemann BC, Fisher MJ. MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus. Neuro Oncol. 2022 11 02; 24(11):1845-1856.  View on PubMed
  4. Niemeyer CM, Rudelius M, Shimamura A, Flotho C, Hasle H, Stieglitz E, Strahm B, Godley LA, Weinberg OK, Orazi A, Calvo KR. Classification of rare pediatric myeloid neoplasia-Quo vadis? Leukemia. 2022 12; 36(12):2947-2948.  View on PubMed
  5. Pearson AD, Allen C, Fangusaro J, Hutter C, Witt O, Weiner S, Reaman G, Russo M, Bandopadhayay P, Ahsan S, Barone A, Barry E, de Rojas T, Fisher M, Fox E, Bender JG, Gore L, Hargrave D, Hawkins D, Kreider B, Langseth AJ, Lesa G, Ligas F, Marotti M, Marshall LV, Nasri K, Norga K, Nysom K, Pappo A, Rossato G, Scobie N, Smith M, Stieglitz E, Weigel B, Weinstein A, Viana R, Karres D, Vassal G. Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration. Eur J Cancer. 2022 Dec; 177:120-142.  View on PubMed
  6. Imaizumi T, Meyer J, Wakamatsu M, Kitazawa H, Murakami N, Okuno Y, Yoshida T, Sajiki D, Hama A, Kojima S, Takahashi Y, Loh M, Stieglitz E, Muramatsu H. Clinical parameter-based prediction of DNA methylation classification generates a prediction model of prognosis in patients with juvenile myelomonocytic leukemia. Sci Rep. 2022 08 30; 12(1):14753.  View on PubMed
  7. Smith SM, Lee A, Tong S, Leung S, Hongo H, Rivera J, Sweet-Cordero A, Michlitsch J, Stieglitz E. Detection of a GLIS3 fusion in an infant with AML refractory to chemotherapy. Cold Spring Harb Mol Case Stud. 2022 Aug 04.  View on PubMed
  8. Lu KL, Menke JR, Ng D, Ruiz-Cordero R, Marinoff A, Stieglitz E, Gollapudi S, Singh K, Ohgami RS, Vohra P. Cytomorphologic features of pediatric-type follicular lymphoma on fine needle aspiration biopsy: case series and a review of the literature. J Am Soc Cytopathol. 2022 Sep-Oct; 11(5):281-294.  View on PubMed
  9. Ramdas B, Yuen LD, Palam LR, Patel R, Pasupuleti SK, Jideonwo V, Zhang J, Maguire C, Wong E, Kanumuri R, Zhang C, Sandusky G, Chan RJ, Zhang C, Stieglitz E, Haneline L, Kapur R. Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells. Mol Ther. 2022 07 06; 30(7):2505-2521.  View on PubMed
  10. Miltiadous O, Petrova-Drus K, Kaicker S, Mathew S, Kluk M, Geyer JT, Rodriguez-Sanchez I, Bouvier N, Inghirami G, Stieglitz E, Khedoudja N, Benayed R, Richardson M, Anderson W, Benhamida J, You D, Londono D, Kung AL, Prockop SE, Roshal M, Zhang Y, Shukla N. Successful treatment and integrated genomic analysis of an infant with FIP1L1-RARA fusion-associated myeloid neoplasm. Blood Adv. 2022 02 22; 6(4):1137-1142.  View on PubMed
  11. Yan Y, Dong L, Chen C, Bunting KD, Li Q, Stieglitz E, Loh ML, Qu CK. JMML tumor cells disrupt normal hematopoietic stem cells by imposing inflammatory stress through overproduction of IL-1β. Blood Adv. 2022 01 11; 6(1):200-206.  View on PubMed
  12. 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. Haematologica. 2022 01 01; 107(1):178-186.  View on PubMed
  13. Kitazawa H, Okuno Y, Muramatsu H, Aoki K, Murakami N, Wakamatsu M, Suzuki K, Narita K, Kataoka S, Ichikawa D, Hamada M, Taniguchi R, Kawashima N, Nishikawa E, Narita A, Nishio N, Hama A, Loh ML, Stieglitz E, Kojima S, Takahashi Y. Simple and robust methylation test for risk stratification of patients with juvenile myelomonocytic leukemia. Blood Adv. 2021 12 28; 5(24):5507-5518.  View on PubMed
  14. Wintering A, Smith S, Fuh B, Rangaswami A, Dahl G, Chien M, Gruber TA, Dang J, Li LS, Lenzen A, Savelli S, Dvorak CC, Agrawal AK, Stieglitz E. Therapy-related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature. Pediatr Blood Cancer. 2022 05; 69(5):e29499.  View on PubMed
  15. Wintering A, Dvorak CC, Stieglitz E, Loh ML. Juvenile myelomonocytic leukemia in the molecular era: a clinician's guide to diagnosis, risk stratification, and treatment. Blood Adv. 2021 11 23; 5(22):4783-4793.  View on PubMed
  16. Bogdan Popescu, Carlos Stahlhut, Theodore C. Tarver, Timothy T. Ferng, Cheryl Peretz, Sydney Wishner, Paul Phojanakong, Veronica Steri, Eric B. Wong, Jose M. Rivera, Elliot Stieglitz, Catherine C. Smith. Allosteric SHP2 Inhibitor RMC4550 Synergizes with Venetoclax in FLT3 and KIT Mutant Acute Myeloid Leukemia. Blood. 2021 Nov 5; 138(Supplement 1):2231-2231.  View on PubMed
  17. Elliot Stieglitz, Mignon L. Loh, Julia Meyer, Chujing Zhang, Donald A Barkauskas, David Hall, Elizabeth Fox, Brenda J. Weigel. MEK Inhibition Demonstrates Activity in Relapsed, Refractory Patients with Juvenile Myelomonocytic Leukemia: Results from COG Study ADVL1521. Blood. 2021 Nov 5; 138(Supplement 1):3679-3679.  View on PubMed
  18. Santhosh Kumar Pasupuleti, Baskar Ramdas, Kai Yang, Chujing Zhang, Elliot Stieglitz, Reuben Kapur. Targeting M2-Tumor Associated Macrophages By Arginase-1 and PD-L1 in Regulating Juvenile Myelomonocytic Leukemia (JMML) Development and Relapse. Blood. 2021 Nov 5; 138(Supplement 1):1471-1471.  View on PubMed
  19. Morales CE, Stieglitz E, Kogan SC, Loh ML, Braun BS. Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia. Blood Adv. 2021 09 28; 5(18):3587-3591.  View on PubMed
  20. 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. J Pediatr Hematol Oncol. 2021 08 01; 43(6):e808-e811.  View on PubMed

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