Background: Juvenile myelomonocytic leukaemia (JMML) and chronic myelomonocytic leukaemia (CMML) are myelodysplastic myeloproliferative (MDS/MPN) neoplasms with unfavourable prognosis and without effective chemotherapy treatment. Trabectedin is a DNA minor groove binder acting as a modulator of transcription and interfering with DNA repair mechanisms; it causes selective depletion of cells of the myelomonocytic lineage. We hypothesised that trabectedin might have an antitumour effect on MDS/MPN. Methods: Malignant CD14+ monocytes and CD34+ haematopoietic progenitor cells were isolated from peripheral blood/bone marrow mononuclear cells. The inhibition of CFU-GM colonies and the apoptotic effect on CD14+ and CD34+ induced by trabectedin were evaluated. Trabectedin's effects were also investigated in vitro on THP-1, and in vitro and in vivo on MV-4-11 cell lines. Results: On CMML/JMML cells, obtained from 20 patients with CMML and 13 patients with JMML, trabectedin - at concentration pharmacologically reasonable, 1-5 nM - strongly induced apoptosis and inhibition of growth of haematopoietic progenitors (CFU-GM). In these leukaemic cells, trabectedin downregulated the expression of genes belonging to the Rho GTPases pathway (RAS superfamily) having a critical role in cell growth and cytoskeletal dynamics. Its selective activity on myelomonocytic malignant cells was confirmed also on in vitro THP-1 cell line and on in vitro and in vivo MV-4-11 cell line models. Conclusions: Trabectedin could be good candidate for clinical studies in JMML/CMML patients.
Romano, M., della Porta, M., Gallì, A., Panini, N., Licandro, S., Bello, E., et al. (2017). Antitumour activity of trabectedin in myelodysplastic/myeloproliferative neoplasms. BRITISH JOURNAL OF CANCER, 116(3), 335-343.
|Citazione:||Romano, M., della Porta, M., Gallì, A., Panini, N., Licandro, S., Bello, E., et al. (2017). Antitumour activity of trabectedin in myelodysplastic/myeloproliferative neoplasms. BRITISH JOURNAL OF CANCER, 116(3), 335-343.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Antitumour activity of trabectedin in myelodysplastic/myeloproliferative neoplasms|
|Autori:||Romano, M; della Porta, M; Gallì, A; Panini, N; Licandro, S; Bello, E; Craparotta, I; Rosti, V; Bonetti, E; Tancredi, R; Rossi, M; Mannarino, L; Marchini, S; Porcu, L; Galmarini, C; Zambelli, A; Zecca, M; Locatelli, F; Cazzola, M; Biondi, A; Rambaldi, A; Allavena, P; Erba, E; D'Incalci, M|
|Data di pubblicazione:||2017|
|Rivista:||BRITISH JOURNAL OF CANCER|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/bjc.2016.424|
|Appare nelle tipologie:||01 - Articolo su rivista|