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EnglishAcute myeloid leukemia (AML) withFLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts forFLT3-ITD-positivity. The aim of this study was to characterize the distribution ofFLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture ofFLT3-ITD(mut)AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients withFLT3-ITD(mut)AML (n = 12). A higherFLT3-ITD(mut)load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/-,CD25-,CD99low/-) (p = 0.0005) and mononuclear cells (MNCs) (p < 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higherFLT3-ITD(mut)burden was also observed in LPCs of AML patients with a smallFLT3-ITD(mut)clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows thatFLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target inFLT3-ITD(mut)AML.
Travaglini, S., Angelini, D.F., Alfonso, V., Guerrera, G., Lavorgna, S., Divona, M., et al. (2020). Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells. BLOOD CANCER JOURNAL, 10(8), 85.
| Tipologia: | Articolo su rivista |
| Citazione: | Travaglini, S., Angelini, D.F., Alfonso, V., Guerrera, G., Lavorgna, S., Divona, M., et al. (2020). Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells. BLOOD CANCER JOURNAL, 10(8), 85. |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore MED/15 |
| Revisione (peer review): | Esperti anonimi |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s41408-020-00352-9 |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 25-ago-2020 |
| Titolo: | Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells |
| Autori: | |
| Autori: | Travaglini, S; Angelini, DF; Alfonso, V; Guerrera, G; Lavorgna, S; Divona, M; Nardozza, AM; Consalvo, MI; Fabiani, E; De Bardi, M; Neri, B; Forghieri, F; Marchesi, F; Paterno, G; Cerretti, R; Barragan, E; Fiori, V; Dominici, S; Del Principe, MI; Venditti, A; Battistini, L; Arcese, W; Lo-Coco, F; Voso, MT; Ottone, T |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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