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https://hdl.handle.net/2440/71906
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dc.contributor.author | Esposito, N. | - |
dc.contributor.author | Colavita, I. | - |
dc.contributor.author | Quintarelli, C. | - |
dc.contributor.author | Sica, A. | - |
dc.contributor.author | Peluso, A. | - |
dc.contributor.author | Luciano, L. | - |
dc.contributor.author | Picardi, M. | - |
dc.contributor.author | Vecchio, L. | - |
dc.contributor.author | Buonomo, T. | - |
dc.contributor.author | Hughes, T. | - |
dc.contributor.author | White, D. | - |
dc.contributor.author | Radich, J. | - |
dc.contributor.author | Russo, D. | - |
dc.contributor.author | Branford, S. | - |
dc.contributor.author | Saglio, G. | - |
dc.contributor.author | Vaz de Melo, J. | - |
dc.contributor.author | Martinelli, R. | - |
dc.contributor.author | Ruoppolo, M. | - |
dc.contributor.author | Kalebic, T. | - |
dc.contributor.author | Martinelli, G. | - |
dc.contributor.author | et al. | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Blood, 2011; 118(13):3634-3644 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.issn | 1528-0020 | - |
dc.identifier.uri | http://hdl.handle.net/2440/71906 | - |
dc.description.abstract | We 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. | - |
dc.description.statementofresponsibility | Nicola Esposito... Timothy P. Hughes... Deborah White... Susan Branford... Junia V. Melo... et al. | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Hematology | - |
dc.rights | © 2011 by The American Society of Hematology | - |
dc.source.uri | http://dx.doi.org/10.1182/blood-2011-03-341073 | - |
dc.subject | Cell Line, Tumor | - |
dc.subject | K562 Cells | - |
dc.subject | Philadelphia Chromosome | - |
dc.subject | Humans | - |
dc.subject | Benzamides | - |
dc.subject | Piperazines | - |
dc.subject | Pyrimidines | - |
dc.subject | Antineoplastic Agents | - |
dc.subject | Protein Kinase Inhibitors | - |
dc.subject | Gene Expression Regulation, Leukemic | - |
dc.subject | Drug Resistance, Neoplasm | - |
dc.subject | Adult | - |
dc.subject | Aged | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | - |
dc.subject | Protein Tyrosine Phosphatase, Non-Receptor Type 6 | - |
dc.subject | Biomarkers, Pharmacological | - |
dc.subject | Young Adult | - |
dc.subject | Biomarkers, Tumor | - |
dc.subject | Imatinib Mesylate | - |
dc.title | SHP-1 expression accounts for resistance to imatinib treatment in Philadelphia chromosome-positive cells derived from patients with chronic myeloid leukemia | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1182/blood-2011-03-341073 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509] | - |
dc.identifier.orcid | White, D. [0000-0003-4844-333X] | - |
dc.identifier.orcid | Branford, S. [0000-0002-1964-3626] [0000-0002-5095-7981] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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