Clinical and prognostic significance of 3q26 rearrangements and other chromosome 3 abnormalities in chronic myelogenous leukemia in era of tyrosine kinase inhibitors

Abstract

Chromosome 3q26.2 abnormalities in acute myeloid leukemia (AML), 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 CML patients in the era of TKI therapy. Chromosome 3 abnormalities were observed in 116 of 2013 (5.8%) cases. These cases were divided into five 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 chromosome 3, 18%. In all, 3q26.2 rearrangements were the most common chromosome 3 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 TKIs treatment and no patients achieved a long-term sustainable response at cytogenetic or molecular level. Compared to other chromosomal abnormalities in CML, patients with 3q26.2 rearrangements had a 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.