Morel Frédéric, Bris Marie-Josée Le, Herry Angèle, Calvez Geneviève Le, Marion Véronique, Abgrall Jean-François, Berthou Christian, Braekeleer Marc De
Faculté de Médecine, Université de Bretagne Occidentale, Brest.
Eur J Haematol. 2003 Apr;70(4):235-9. doi: 10.1034/j.1600-0609.2003.00046.x.
Amplification of the bcr-abl fusion gene has recently been associated with resistance to imatinib therapy in chronic myeloid leukemia (CML). A 55-yr-old man was diagnosed with Philadelphia (Ph) chromosome-positive CML. Resistance to interferon treatment and occurrence of blastic phase lead to the decision of imatinib therapy. After two autologous stem cell transplantation, the patient reverted to chronic phase with a decrease in the proportion of Ph chromosome-positive cells under imatinib. A second blastic phase occurred 4 months after transplantation, of which the patient died. Cytogenetic studies, including fluorescent in situ hybridization, showed a (9;22)(q34;q11) translocation and one bcr-abl fusion gene during the whole evolution, but for the last 2 months. Bcr-abl gene amplification (over 25 copies) was noted while banding cytogenetics showed a karyotype of 55-62 chromosomes with multiple double minutes (dmin). To the best of our knowledge, dmin containing amplified bcr-abl gene has never been reported in patients with CML. Therefore, although we cannot exclude that the gene amplification was strictly associated with disease progression, our data may suggest that the amplification resulted in resistance to imatinib.
bcr-abl融合基因的扩增最近被认为与慢性髓性白血病（CML）患者对伊马替尼治疗的耐药性有关。一名55岁男性被诊断为费城（Ph）染色体阳性的CML。由于对干扰素治疗耐药且进入急变期，决定给予伊马替尼治疗。两次自体干细胞移植后，患者在伊马替尼治疗下恢复至慢性期，Ph染色体阳性细胞比例下降。移植后4个月出现第二次急变期，患者死亡。细胞遗传学研究，包括荧光原位杂交，在整个病程中均显示有（9；22）（q34；q11）易位和一个bcr-abl融合基因，但在最后2个月除外。观察到bcr-abl基因扩增（超过25个拷贝），而染色体显带分析显示核型为55 - 62条染色体，伴有多个双微体（dmin）。据我们所知，含有扩增bcr-abl基因的dmin在CML患者中从未有过报道。因此，尽管我们不能排除基因扩增与疾病进展密切相关，但我们的数据可能提示扩增导致了对伊马替尼的耐药。
