Role of treatment in the appearance and selection of BCR-ABL1 kinase domain mutations

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Publikace nespadá pod Filozofickou fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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RÁZGA Filip JURČEK Tomáš ŽÁČKOVÁ Daniela DVOŘÁKOVÁ Dana TOŠKOVÁ Martina JEŽÍŠKOVÁ Ivana MAYER Jiří RÁČIL Zdeněk

Rok publikování 2012
Druh Článek v odborném periodiku
Časopis / Zdroj Molecular diagnosis and therapy
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Obor Onkologie a hematologie
Klíčová slova BCR-ABL1; gene mutations; CML
Přiložené soubory
Popis Our data show that pretreatment with non-specific non-TKI drugs prior to TKI therapy does not preferentially select for initial BCR-ABL1 KD mutations, in contrast to first-line imatinib therapy, which shows a clear predominance of T315I or P-loop mutations compared with mutations located in other KD regions. In addition, the median time to detection of P-loop mutations was substantially shorter in patients treated with first-line imatinib than in those pretreated with non-TKI drugs. Furthermore, analysis of CML patients who had recurrent resistance to TKI therapy revealed possible therapy-driven selection of BCRABL1 KD mutations. Finally, we confirm the previously described poor prognosis of CML patients with mutations in the BCR-ABL1 KD, since 40.0% of our CML patients who harbored a BCR-ABL1 KD mutation died from CML while receiving TKI treatment. Moreover, among the patients who are still on treatment, 27.8%have already progressed. Our data also confirm the unique position of the T315I mutation with respect to its strong resistance to currently approved TKIs.
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