Kinase domain mutations of BCR-ABL identified at diagnosis before imatinib-based therapy are associated with progression in patients with high Sokal risk chronic phase chronic myeloid leukemia

Angelo M. Carella, Anna Garuti, Gabriella Cirmena, Gioacchino Catania, Ilaria Rocco, Claudia Palermo, Gianmatteo Pica, Ivana Pierri, Maurizio Miglino, Alberto Ballestrero, Marco Gobbi, Franco Patrone

Research output: Contribution to journalArticle

Abstract

Acquired resistance to imatinib in the advanced phase of chronic myeloid leukemia (CML) has been associated with mutations in the kinase domain (KD) of BCR-ABL. On the contrary, the prognostic implication of KD mutations in early chronic phase (CP) patients at diagnosis before imatinib-based therapy has not yet been established. We have reviewed the status of mutations in 43 patients with early CP-CML on the samples collected at diagnosis. Mutations were identified by direct sequencing (DS) with BidDye Terminator v 1.1. cycle sequencing kit and analyzed with a 3130 ABI capillary electrophoresis system. Eight out 13 (61.5) high Sokal risk patients showed the following mutations: Y253C, S265R, E255K, F359Y, N374S, E255V, E255V, E255V. Three patients progressed during imatinib and second-line inhibitors and died of blastic phase CML at 23, 33, and 69 months. Another patient with intermediate Sokal risk showed D363G mutation at diagnosis, progressed under imatinib, was allografted and he is now alive in major molecular remission (MMR). No low-risk patient carried KD mutation at diagnosis. In conclusion, KD mutations conferring high-level imatinib resistance are present in patients with de novo CML and in some of them lead to disease progression.

Original languageEnglish
Pages (from-to)275-278
Number of pages4
JournalLeukemia and Lymphoma
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 2010

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Keywords

  • Chronic myeloid leukemia
  • Disease progression
  • Kinase domain mutations at diagnosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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