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ACUTE MYELOID LEUKEMIA

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

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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.

References

  1. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–52.

    Article  Google Scholar 

  2. Thomas D, Majeti R. Biology and relevance of human acute myeloid leukemia stem cells. Blood. 2017;129:1577–85.

    CAS  Article  Google Scholar 

  3. Angelini DF, Ottone T, Guerrera G, Lavorgna S, Cittadini M, Buccisano F, et al. A leukemia-associated CD34/CD123/CD25/CD99+immunophenotype identifies FLT3-mutated clones in acute myeloid Leukemia. Clin Cancer Res. 2015;21. https://doi.org/10.1158/1078-0432.CCR-14-3186.

  4. Travaglini S, Angelini DF, Alfonso V, Guerrera G, Lavorgna S, Divona M, et al. Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells. Blood Cancer J. 2020;10:85.

    Article  Google Scholar 

  5. Manara MC, Pasello M, Scotlandi K. CD99: a cell surface protein with an oncojanus role in tumors. Genes. 2018;9. https://doi.org/10.3390/genes9030159.

  6. Travaglini S, Angelini DF, Alfonso V, Guerrera G, Lavorgna S, Divona M, et al. Characterization of FLT3-ITD(mut) acute myeloid leukemia: molecular profiling of leukemic precursor cells. Blood Cancer J. 2003;21:759–806.

    Google Scholar 

  7. Ottone T, Zaza S, Divona M, Hasan SK, Lavorgna S, Laterza S, et al. Identification of emerging FLT3 ITD-positive clones during clinical remission and kinetics of disease relapse in acute myeloid leukaemia with mutated nucleophosmin. Br J Haematol. 2013;161:533–40.

    CAS  Article  Google Scholar 

  8. Hahn JH, Kim MK, Choi EY, Kim SH, Sohn HW, Ham DI, et al. CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion. J Immunol. 1997;159:2250–8.

    CAS  PubMed  Google Scholar 

  9. Vaikari VP, Du Y, Wu S, Zhang T, Metzeler K, Batcha AMN, et al. Clinical and preclinical characterization of CD99 isoforms in acute myeloid leukemia. Haematologica. 2020;105:999–1012.

    CAS  Article  Google Scholar 

  10. Chung SS, Bernard G, Lollini P-L, Nanni P, Zuntini M, Landuzzi L, et al. CD99 is a therapeutic target on disease stem cells in myeloid malignancies. Sci Transl Med. 2017;17:1910–21.

    Google Scholar 

  11. Tavakkoli M, Chung SS, Park CY. Do preclinical studies suggest that CD99 is a potential therapeutic target in acute myeloid leukemia and the myelodysplastic syndromes? Expert Opin Ther Targets. 2018;22:381–3.

    CAS  Article  Google Scholar 

  12. Scotlandi K, Zuntini M, Manara MC, Sciandra M, Rocchi A, Benini S, et al. CD99 isoforms dictate opposite functions in tumour malignancy and metastases by activating or repressing c-Src kinase activity. Oncogene. 2007;26:6604–18.

    CAS  Article  Google Scholar 

  13. Costello RT, Mallet F, Gaugler B, Sainty D, Arnoulet C, Gastaut J-A, et al. Human acute myeloid Leukemia CD34+/CD38− progenitor cells have decreased sensitivity to chemotherapy and fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res. 2000;60:4403 LP–4411.

    Google Scholar 

Download references

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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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.

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Correspondence to Maria Teresa Voso.

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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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  • DOI: https://doi.org/10.1038/s41375-022-01566-5

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