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ACUTE MYELOID LEUKEMIA

CD99 as a novel therapeutic target on leukemic progenitor cells in FLT3-ITDmut AML

Leukemia volume 36, pages 1685–1688 (2022)Cite this article

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Acute Myeloid Leukemia with FLT3 internal tandem duplication mutations (FLT3-ITDmut AML) is an aggressive leukemia characterized by heterogeneous genetic landscape [1]. Despite significant advances in AML therapy, the relapse rate remains high, due to the emergence of resistant clones, possibly involving leukemic stem cells (LSCs) [2]. This highlights the unmet need for deeper understanding of the molecular and immunophenotypic landscape of LSCs in FLT3-ITDmut AML. We previously identified a population of leukemic precursor cells (LPCs), present at the time of initial AML diagnosis, characterized by the CD34/CD123/CD25/CD99+ immunophenotype, and predictive for FLT3-ITDmut positivity [3]. In particular, these cells overexpress CD99 antigen, which may represent a target for monoclonal antibody (mAb) treatment [4].

CD99 is a transmembrane glycoprotein involved in crucial biological processes, including cell adhesion, migration, invasion, death and differentiation, pointing to a multifactorial role in oncogenesis [5]. Our study aimed at providing new insights on CD99 role in FLT3-ITDmut AMLs, dissecting the potential interplay with the FLT3 receptor, its involvement in disease progression and resistance, and as a promising new therapeutic target.

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Fig. 1: Analysis of CD99 expression in primary AML samples and BM-MNC from healthy donors.
Fig. 2: Effects of the anti-CD99 mAb in primary AML blasts and cell lines.

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Acknowledgements

This work was supported by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC. A detailed description of the MYNERVA project is available at http://www.progettoagimm.it.), by GR-2018-12365529-Santa Lucia to TO, by PRIN grant N. 2017WXR7ZT to MTV, by Ministero della Salute, Rome, Italy (Finalizzata 2018, NET-2018-12365935, Personalized medicine program on myeloid neoplasms: characterization of the patient’s genome for clinical decision making and systematic collection of real world data to improve quality of health care) to MTV and AIRC IG 2018 - ID. 21406 project to FF

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  1. These authors contributed equally: Serena Travaglini, Tiziana Ottone.

Authors and Affiliations

  1. Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy

    Serena Travaglini, Tiziana Ottone, Nelida Ines Noguera, Silvia Antonelli, Maria Antonietta Irno Consalvo, Mariadomenica Divona, Raffaele Palmieri, Gottardo De Angelis, Francesco Buccisano, Adriano Venditti & Maria Teresa Voso

  2. Santa Lucia Foundation, I.R.C.C.S., Neuro-Oncohematology, Rome, Italy

    Tiziana Ottone, Daniela Francesca Angelini, Nelida Ines Noguera, Marco De Bardi, Cristina Banella, Luca Battistini & Maria Teresa Voso

  3. Diatheva srl, 61030, Pesaro-Urbino, Italy

    Valentina Fiori, Sabrina Dominici & Mauro Magnani

  4. Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, Rome, Italy

    Martyna Śniegocka, Silvia Masciarelli & Francesco Fazi

  5. Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Francesco Marchesi

  6. Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Hearth, Rome, Italy

    Marco Pieraccioli

Authors
  1. Serena Travaglini
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  2. Tiziana Ottone
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  9. Maria Antonietta Irno Consalvo
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  21. Luca Battistini
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  22. Mauro Magnani
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  23. Maria Teresa Voso
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Contributions

ST, TO, DFA, VF, SD, NIN, LB, MM and MTV made substantial contributions to conception, design of the study, and analysis and interpretation of the data; MS, SA, CB, MAIC, MDB, MD, MP, performed the experiments, FM, SM, FF, RP, GDA, FB, AV acquired and analyzed the data; all authors revised and approved the manuscript.

Corresponding author

Correspondence to Maria Teresa Voso.

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The authors declare no competing interests.

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Travaglini, S., Ottone, T., Angelini, D.F. et al. CD99 as a novel therapeutic target on leukemic progenitor cells in FLT3-ITDmut AML. Leukemia 36, 1685–1688 (2022). https://doi.org/10.1038/s41375-022-01566-5

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