Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloThe WNT Pathway Is Relevant for the BCR-ABL1-Independent Resistance in Chronic Myeloid Leukemia
Anno di pubblicazione2019
Autore/iGrassi, Susanna; Palumbo, Sara; Mariottit, Veronica; Liberati, Diego; Guerrini, Francesca; Ciabatti, Elena; Salehzadeh, Serena; Barate, Claudia; Balducci, Serena; Ricci, Federica; Buda, Gabriele; Iovino, Lorenzo; Mazziotta, Francesco; Ghio, Francesco; Ercolano, Giacomo; Di Paolo, Antonello; Cecchettini, Antonella; Baldini, Chiara; Mattii, Letizia; Pellegrini, Silvia; Petrini, Mario; Galimberti, Sara
Affiliazioni autoriUniv Pisa; Univ Siena; Univ Pisa; Univ Pisa; Natl Res Council Italy; Univ Pisa; Univ Pisa
Autori CNR e affiliazioni
  • inglese
AbstractNotwithstanding the introduction of Tyrosine Kinase Inhibitors (TKIs) revolutionized the outcome of Chronic Myeloid Leukemia (CML), one third of patients still suspends treatment for failure response. Recent research demonstrated that several BCR/ABL1-independent mechanisms can sustain resistance, but the relationship between these mechanisms and the outcome has not yet been fully understood. This study was designed to evaluate in a "real-life" setting if a change of expression of several genes involved in the WNT/BETA-CATENIN, JAK-STAT, and POLYCOMB pathways might condition the outcome of CML patients receiving TKIs. Thus, the expression of 255 genes, related to the aforementioned pathways, was measured by quantitative PCR after 6 months of therapy and compared with levels observed at diagnosis in 11 CML patients, in order to find possible correlations with quality of response to treatment and event-free-survival (EFS). These results were then re-analyzed by the principal component method (PCA) for tempting to better cluster resistant cases. After 12 months of therapy, 6 patients achieved an optimal response and 5 were "resistant;" after application of both statistical methods, it was evident that in all pathways a significant overall up-regulation occurred, and that WNT was the pathway mostly responsible for the TKIs resistance. Indeed, 100% of patients with a "low" up-regulation of this pathway achieved an optimal response vs. 33% of those who showed a "high" gene over-expression (p = 0.016). Analogously, the 24-months EFS resulted significantly influenced by the degree of up-regulation of the WNT signaling: all patients with a "low" up-regulation were event-free vs. 33% of those who presented a "high" gene expression (p = 0.05). In particular, the PCA analysis confirmed the role of WNT pathway and showed that the most significantly up-regulated genes with negative prognostic value were DKK, WNT6, WISP1, and FZD8. In conclusion, our results sustain the need of a wide and multitasking approach in order to understand the resistance mechanisms in CML.
Lingua abstractinglese
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Pagine totali12
RivistaFrontiers in oncology
Attiva dal 2011
Editore: Frontiers Editorial Office, - Lausanne
Paese di pubblicazione: Svizzera
Lingua: inglese
ISSN: 2234-943X
Titolo chiave: Frontiers in oncology
Titolo proprio: Frontiers in oncology
Titolo abbreviato: Front. oncol.
Numero volume della rivista9
Fascicolo della rivista-
Verificato da refereeSì: Internazionale
Stato della pubblicazionePublished version
Indicizzazione (in banche dati controllate)
  • ISI Web of Science (WOS) (Codice:000473054600001)
Parole chiaveWNT/beta-catenin, PcGs, JAK/STAT, CML, BCR/ABL1-independent resistance, PCA
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Strutture CNR
  • IEIIT — Istituto di elettronica e di ingegneria dell'informazione e delle telecomunicazioni
Moduli/Attività/Sottoprogetti CNR
  • DIT.AD007.007.004 : ICSB - Information and Control for Systems Biology
Progetti Europei-