Variant Philadelphia translocations: Molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA working party on CML analysis

Giulia Marzocchi, Fausto Castagnetti, Simona Luatti, Carmen Baldazzi, Monica Stacchini, Gabriele Gugliotta, Marilina Amabile, Giorgina Specchia, Mario Sessarego, Ursula Giussani, Laura Valori, Giancarlo Discepoli, Anna Montaldi, Alessandra Santoro, Laura Bonaldi, Giovanni Giudici, Anna Maria Cianciulli, Francesca Giacobbi, Francesca Palandri, Fabrizio PaneGiuseppe Saglio, Giovanni Martinelli, Michele Baccarani, Gianantonio Rosti, Nicoletta Testoni

Research output: Contribution to journalArticle

Abstract

Variant Philadelphia (Ph) chromosome translocations have been reported in 5%-10% of patients with newly diagnosed chronic myeloid leukemia (CML). Variant translocations may involve one or more chromosomes in addition to 9 and 22, and can be generated by 2 different mechanisms, 1-step and 2-step rearrangements, as revealed by fluorescence in situ hybridization. The prognostic significance of the occurrence of variant translocations has been discussed in previous studies. The European LeukemiaNet recommendations do not provide a "warning" for patients with variant translocations, but there is limited information about their outcome after therapy with tyrosine kinase inhibitors. To identify the role of variant translocations in early chronic phase (CP) CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective imatinib trials of the Gruppo ItalianoMalattie EMatologiche dell'Adulto (GIMEMA) Working Party on CML. Variant translocations occurred in 30 patients (5%). Our data show that the presence of variant translocations has no impact on the cytogenetic and molecular response or on outcome, regardless of the involvement of different mechanisms, the number of involved chromosomes, or the presence of deletions. Therefore, we suggest that patients with variant translocations do not constitute a "warning" category in the imatinib era. This study is registered at www.clinicaltrials.gov as NCT00514488 and NCT00510926.

Original languageEnglish
Pages (from-to)6793-6800
Number of pages8
JournalBlood
Volume117
Issue number25
DOIs
Publication statusPublished - Jun 23 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Marzocchi, G., Castagnetti, F., Luatti, S., Baldazzi, C., Stacchini, M., Gugliotta, G., Amabile, M., Specchia, G., Sessarego, M., Giussani, U., Valori, L., Discepoli, G., Montaldi, A., Santoro, A., Bonaldi, L., Giudici, G., Cianciulli, A. M., Giacobbi, F., Palandri, F., ... Testoni, N. (2011). Variant Philadelphia translocations: Molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA working party on CML analysis. Blood, 117(25), 6793-6800. https://doi.org/10.1182/blood-2011-01-328294