Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloThe Wnt Pathway is Relevant for the BCR-ABL-1 Independent Resistance in Chronic Myeloid Leukemia
Anno di pubblicazione2019
Autore/iSusanna Grassi1*, Sara Palumbo2, Veronica Mariotti3, Diego Liberati4, Francesca Guerrini5, Elena Ciabatti5, Serena Salehzadeh5, Claudia Baratè5, Serena Balducci5, Federica Ricci5, Gabriele Buda5, Lorenzo Iovino5, Francesco Mazziotta5, Fracesco Ghio5, Giacomo Ercolano5, Antonello Di Paolo6, Antonela Cecchettini3, Chiara Baldini6, Letizia Mattii3, Silvia Pellegrini3, Mario Petrini5, Sara Galimberti5*
Affiliazioni autori1Department of Medical Biotecmologies, University of Siena, Italy, 2Department of Surgical, Medical, Molecular and Critical Pathology, University of Pisa, Italy, 3Department of Clinical and Experimental Medicine, University of Pisa, Italy, 4National Research Council Research Area Milan, Italy, 5Division of Hematolog , University Hospital of Pisa, Italy, 6University of Pisa, Italy
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/BETACATENIN, 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 versus 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 versus 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.
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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.
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Stato della pubblicazionePublished version
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Parole chiaveWnt/?-catenin, JAK/STAT, PcGs, BCR/ABL1-indpedent resistane, CML, 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-