Johansson B, Fioretos T, Billström R, Mitelman F
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Leukemia. 1996 Jul;10(7):1134-8.
The cytogenetic evolution of 32 Philadelphia (Ph)-positive chronic myeloid leukemias (CML) receiving interferon-alpha (IFN-alpha) therapy was compared to the patterns in untreated CML and cases treated with busulfan (Bu), hydroxyurea (Hy), and allogeneic bone marrow transplantation (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) were recurrent; a frequency significantly higher than in CML without therapy 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 group. 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-alpha, directly or indirectly, can induce clones with aberrant chromosomal evolution patterns to evolve and proliferate, but the mechanisms underlying these cytogenetic peculiarities remain to be elucidated.
将接受α干扰素（IFN-α）治疗的32例费城染色体（Ph）阳性慢性髓性白血病（CML）的细胞遗传学演变与未经治疗的CML以及接受白消安（Bu）、羟基脲（Hy）和异基因骨髓移植（BMT）治疗的病例模式进行了比较。接受IFN-α治疗的CML患者中有一半至少有一个众所周知的主要或次要途径畸变，而16例表现出异常的继发性异常，其中只有del(7p)和del(13q)是复发的；其频率显著高于未治疗的CML或接受Bu和Hy治疗后的CML（P < 0.001），但与BMT后发现的频率相似。与未治疗组、Bu组和Hy组相比，IFN-α组中具有细胞遗传学上不同亚克隆的病例发生率也更高，即除t(9;22)外还具有不相关畸变的细胞群体（P < 0.01），但与BMT后组相似。最后，32例接受IFN-α治疗的CML中有14例在慢性期就已出现细胞遗传学演变；同样，其发生率高于未治疗组、Bu组和Hy组（P < 0.001），但与BMT后组无差异。这些发现有力地表明，IFN-α可直接或间接诱导具有异常染色体演变模式的克隆发生演变和增殖，但其细胞遗传学特性背后的机制仍有待阐明。
