Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Wei Wang, Jorge E. Cortes, Pei Lin, Michael W. Beaty, Di Ai, Hesham M. Amin, Timothy J. McDonnell, Chi Young Ok, Hagop M. Kantarjian, L. Jeffrey Medeiros, Shimin Hu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Chromosome 3q26.2 abnormalities in acute myeloid leukemia, including inv(3)/t(3;3) and t(3;21), have been studied and are associated with a poor prognosis. Their prevalence, response to tyrosine kinase inhibitor (TKI) treatment, and prognostic significance in chronic myelogenous leukemia (CML) are largely unknown. In this study, we explored these aspects using a cohort of 2013 patients with CML diagnosed in the era of TKI therapy. Chromosome 3 abnormalities were observed in 116 (5.8%) of 2013 cases. These cases were divided into 5 distinct groups: A, inv(3)(q21q26.2)/t(3;3)(q21;q26.2), 26%; B, t(3;21)(q26.2;q22), 17%; C, other 3q26.2 rearrangements, 7%; D, rearrangements involving chromosome 3 other than 3q26.2 locus, 32%; and E, gain or loss of partial or whole chromosome3, 18%. In all, 3q26.2 rearrangements were the mostcommonchromosome3 abnormalities (50%, groups A-C). 3q26.2 rearrangements emerged at different leukemic phases. For cases with 3q26.2 rearrangements that initially emerged in chronic or accelerated phase, they had a high rate of transformation to blast phase. Patients with 3q26.2 abnormalities showed a marginal response to TKI treatment, and no patients achieved a long-term sustainable response at a cytogenetic or molecular level. Compared with other chromosomal abnormalities in CML, patients with 3q26.2 rearrangements had poorer overall survival. The presence or absence of other concurrent chromosomal abnormalities did not affect survival in these patients, reflecting the predominant role of 3q26.2 rearrangements in determining prognosis. Interestingly, although heterogeneous, chromosome 3 abnormalities involving non-3q26.2 loci (groups D, E) also conferred a worse prognosis compared with changes involving other chromosomes in this cohort. (Blood. 2015;126(14):1699-1706).

Original languageEnglish (US)
Pages (from-to)1699-1706
Number of pages8
JournalBlood
Volume126
Issue number14
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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