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dc.contributor.authorEsposito, N.en
dc.contributor.authorColavita, I.en
dc.contributor.authorQuintarelli, C.en
dc.contributor.authorSica, A.en
dc.contributor.authorPeluso, A.en
dc.contributor.authorLuciano, L.en
dc.contributor.authorPicardi, M.en
dc.contributor.authorVecchio, L.en
dc.contributor.authorBuonomo, T.en
dc.contributor.authorHughes, T.en
dc.contributor.authorWhite, D.en
dc.contributor.authorRadich, J.en
dc.contributor.authorRusso, D.en
dc.contributor.authorBranford, S.en
dc.contributor.authorSaglio, G.en
dc.contributor.authorVaz de Melo, J.en
dc.contributor.authorMartinelli, R.en
dc.contributor.authorRuoppolo, M.en
dc.contributor.authorKalebic, T.en
dc.contributor.authorMartinelli, G.en
dc.contributor.authoret al.en
dc.identifier.citationBlood, 2011; 118(13):3634-3644en
dc.description.abstractWe prove that the SH2-containing tyrosine phosphatase 1 (SHP-1) plays a prominent role as resistance determinant of imatinib (IMA) treatment response in chronic myelogenous leukemia cell lines (sensitive/KCL22-S and resistant/KCL22-R). Indeed, SHP-1 expression is significantly lower in resistant than in sensitive cell line, in which coimmunoprecipitation analysis shows the interaction between SHP-1 and a second tyrosine phosphatase SHP-2, a positive regulator of RAS/MAPK pathway. In KCL22-R SHP-1 ectopic expression restores both SHP-1/SHP-2 interaction and IMA responsiveness; it also decreases SHP-2 activity after IMAtreatment. Consistently, SHP-2 knocking-down in KCL22-R reduces either STAT3 activation or cell viability after IMA exposure. Therefore, our data suggest that SHP-1 plays an important role in BCR-ABL–independent IMA resistance modulating the activation signals that SHP-2 receives from both BCR/ABL and membrane receptor tyrosine kinases. The role of SHP-1 as a determinant of IMA sensitivity has been further confirmed in 60 consecutive untreated patients with chronic myelogenous leukemia, whose SHP-1 mRNA levels were significantly lower in case of IMA treatment failure (P < .0001). In conclusion, we suggest that SHP-1 could be a new biologic indicator at baseline of IMA sensitivity in patients with chronic myelogenous leukemia.en
dc.description.statementofresponsibilityNicola Esposito... Timothy P. Hughes... Deborah White... Susan Branford... Junia V. Melo... et al.en
dc.publisherAmer Soc Hematologyen
dc.rights© 2011 by The American Society of Hematologyen
dc.subjectCell Line, Tumor; K562 Cells; Philadelphia Chromosome; Humans; Piperazines; Pyrimidines; Antineoplastic Agents; Tumor Markers, Biological; Protein Kinase Inhibitors; Gene Expression Regulation, Leukemic; Drug Resistance, Neoplasm; Adult; Aged; Middle Aged; Female; Male; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Biomarkers, Pharmacological; Young Adulten
dc.titleSHP-1 expression accounts for resistance to imatinib treatment in Philadelphia chromosome-positive cells derived from patients with chronic myeloid leukemiaen
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
dc.identifier.orcidHughes, T. [0000-0002-0910-3730]en
dc.identifier.orcidWhite, D. [0000-0003-4844-333X]en
dc.identifier.orcidBranford, S. [0000-0002-1964-3626]en
Appears in Collections:Medicine publications

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