Additional chromosome abnormalities in chronic myeloid leukemia

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty-four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p < 0.05). In conclusion, we presented the cytogenetic and molecular pattern of CML patients and demonstrated that the additional chromosome abnormality was associated with poor outcome.

摘要慢性骨髓性白血病通常帶有獨特的標記，包括費城染色體和BCR-ABL的基因，然而此病之臨床表現及預後卻往往有很大的差異。因此我們分析慢性骨髓性白血病病患之染色體及基因檢查之結果，來看是否這些資料和臨床表現及預後有相關。共有84位新診斷的慢性骨髓性白血病病人進行分析，而這些病人的治療是依據病患的狀況予以治療。染色體及基因檢查是由病患的骨髓檢體所做之檢查，而病患的臨床表現、治療狀況及預後是由病歷資料回顧所得。於84位病人中有72位是屬於慢性期，有12位是屬於加速期。染色體檢查中有69位 (82.1%)是屬於標準的費城染色體，有6位 (7.2%)是屬於變異的費城染色體，有9位 (10.7%) 是屬於額外染色體變化。基因檢查中有54位(64.3%)是屬於b3a2，有29位(34.5%)是屬於b2a2，有1位是屬於e19a2。病患的臨床表現和不同組的染色體及基因並無差別，但是額外染色體變化卻和病患的加速期有相關。而Imatinib對慢性期病患於一線及二線的治療均有不錯之反應。生存分析中發現年紀愈大、有額外染色體變化、有較高的Sokal分數、對二線的治療反應不佳者有有意義的負面影響(p<0.05)。我們於此報告中顯示了慢性骨髓性白血病病患之染色體及基因變化，且顯示出額外染色體變化對慢性骨髓性白血病有不良之影響。