ABERRANT CYTOGENETIC EVOLUTION PATTERN OF PHILADELPHIA-POSITIVE CHRONIC MYELOID-LEUKEMIA TREATED WITH INTERFERON-ALPHA

The cytogenetic evolution of 32 Philadelphia (Ph)-positive chronic mye loid leukemias (CML) receiving interferon-alpha (IFN-alpha) therapy wa s compared to the patterns In untreated CML and cases treated with bus ulfan (Bu), hydroxyurea (Hy), and allogeneic bone marrow transplantati on (BMT). Half of the CML receiving IFN-alpha had at least one of the well-known major or minor route aberrations whereas 16 cases displayed unusual secondary abnormalities, of which only del(7p) and del(13q) w ere recurrent; a frequency significantly higher than in CML without th erapy or after Bu and Hy treatment (P < 0.001) but similar to the one found post-BMT. The incidence of cases with cytogenetically divergent subclones, ie cell populations with unrelated aberrations in addition to the t(9;22), was also higher in the IFN-alpha group compared to the untreated, Bu and Hy groups (P < 0.01) but similar to the post-BMT gr oup. Finally, 14 of the 32 IFN-alpha-treated CML displayed cytogenetic evolution already during the chronic phase; again a higher incidence than in the untreated, Bu and Hy groups (P < 0.001) but not different from the post-BMT group. These findings strongly indicate that IFN-alp ha, directly or indirectly, can induce clones with aberrant chromosoma l evolution patterns to evolve and proliferate, but the mechanisms und erlying these cytogenetic peculiarities remain to be elucidated.