Coexistence of Trisomy 8 as Both Clonal and Adjunctive Cytogenetic Abnormality in Philadelphia-Positive (Ph+) Chronic Myeloid Leukemia (CML) Patients on Treatment with Tirosine Kinase Inhibitors (TKIs): Report of Two Cases

Background. In the pre-TKIs era, development of Adjunctive Cytogenetic Abnormalities (ACA) within the Ph+ clone, especially trisomy 8 (+8), carried a worse prognosis being considered expression of emergence of a more aggressive clone. With the use of CML-targeted therapy, along with ACA, also Clonal Cytogenetic Abnormalities (CCA) arising in Ph− cells are being reported, whose clinical impact is yet to be fully understood. While ACA is recognized as a sign of resistance to TKIs, CCA seem to carry a different prognostic impact according to the type of abnormality detected (e.g. −7 poor prognosis; +8 apparently irrelevant). So far only sporadic cases carrying both ACA and CCA are reported in literature.

Methods and Results. We describe two CML patients that developed +8 in both Ph+ and Ph− cells during TKIs treatment. In our Department we analyze the response to therapy by cytogenetic analysis (at least every 6 mos) and by peripheral blood FISH and molecular biology (every 3 mos). In the tables we underline only the most interesting analysis for our discussion. Pts 1. Female, age at diagnosis 62 yrs. She was referred from another Center because of imatinib resistance, after having been treated with hydroxyurea (for 27 mos). The subsequent therapeutic and cytogenetic profiles are summarized in Table 1.

Table1

Table 2

Conclusions. In both CML and myelodysplastic syndrome (MDS), ACA +8 is recognized as a negative prognostic factor, conferring a more aggressive behavior to the mutated cell. However, our data and those of larger case series, suggest that this may not be the case when +8 develops in CML pts as CCA. It seems to confer to Ph− cells only a proliferative advantage which enables them to sustain hematopoiesis without development of a “true” MDS and without interfering with the natural history of CML. The emergence of +8 in both Ph+ and Ph− cells seems to suggest that a minority of CML pts may be prone to develop this specific abnormality, either concomitantly or even before emergence of the Ph+ clone.