Publication details

T315I mutations are clustered with advanced phases contrary to other aberrations in CML patients resistant to TKI therapy

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Authors

MALČÍKOVÁ Jitka JURČEK Tomáš RÁZGA Filip DVOŘÁKOVÁ Dana ŽÁČKOVÁ Daniela DARZENTAS Nikos ŠEBEJOVÁ Ludmila ŠMARDOVÁ Jana OLTOVÁ Alexandra JURAČKOVÁ Lenka TRBUŠEK Martin DOUBEK Michael POSPÍŠILOVÁ Šárka MAYER Jiří RÁČIL Zdeněk

Year of publication 2012
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

Citation
Description Various mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML) patients were described. Among them, mutations within BCR-ABL1 kinase domain are the most frequently studied, since they affect binding of TKI molecule. However, mechanisms leading to subsequent progression are still not fully elucidated. Inhibition of BCR-ABL1 by imatinib was suggested to induce p53 pathway, therefore, p53 inactivation could possibly influence therapy response. Beside this, mutations in genes involved in myeloid transformation (e.g. ASXL11 and CBL) were identified, and their role in disease progression is under investigation. Aims. We analyzed genomic aberrations and mutations in BCR-ABL1, TP53, ASXL1 and CBL genes in patients with primary or acquired resistance to TKIs therapy.
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