[Analysis of the Relationship between Cytogenetic Changes and Course Evolution of Patients with CML during TKI Treatment]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):136-140. doi: 10.19746/j.cnki.issn.1009-2137.2020.01.023.
[Article in Chinese]


Objective: To analyze the relationship between cytogenetic changes and the progression in the patients with chronic myeloid leukemia (CML) during the treatment with tyrosine kinase inhibitor (TKI).

Methods: The chromosome G banding of 150 patients with CML treated in our hospital, was carried out to analyze the karyotype by the 24 h short-term culture or direct method of bone marrow cells, and the point mutation of the ABL kinase area was detected, the relationship between cytogenetic changes and the evolution of the disease course was analyzed.

Results: The indirect fluorescence in situ hybridization showed that the BCR-ABL fusion gene of 150 patients was positive, out of which 142 cases showed positive Philadelphia (Ph) (94.67%), 8 cases with Ph negative (5.33%). Among 142 cases with Ph positive on the first diagnosis, and 14 cases (9.86%) with additional chromosome abnormality (9.86%), 4 cases (2.82%) with mutation translocation with 124 cases (87.32%), standard translocation t (9; 22) (q34; Q11) were found. Out of the 14 patients with additional chromosomal abnormalities, 8 cases with "main pathmay" abnormalities, 2 case with -Y abnormalities, and 4 cases with "secondary pathway" abnormalities were observed. During TKI treatment, additional chromosomal abnormalities were found in 46 patients with standard translocation and abnormal number of chromosomes, and the incidence of disease progression and point mutation were higher (P<0.05). Compared with patients with the standard translocation, the disease-free survival rate of the patients diagnosed as CML at 1st visit and with additional chromosome abnormality was significantly decreased (P<0.05), but the overall survival rate showed no significantly different (P>0.05). Compared with patients without additional cvtogenetic aberrations, the disease free and overall survival rate of the patients with additional cytogenetic aberrations during the TKI treatment of CML in chronic phase were significantly decreased (P<0.05).

Conclusion: Some CML patients may have additional chromosomal abnormalities during the onset and development of the disease, and these patients are at higher risk of disease progression.

题目: CML患者在TKI治疗过程中的细胞遗传学变化与病程演进的关系分析.

目的: 分析慢性髓系白血病(CML)患者在酪氨酸激酶抑制剂(TKI)治疗过程中的细胞遗传学变化与病程演进的关系.

方法: 对本院收治的150例初诊CML患者,通过骨髓细胞24 h短期培养法或直接法,行染色体G显带技术核型分析;经ABL激酶区点突变检测,分析细胞遗传学变化与其病程演进的相关性.

结果: 间接荧光原位杂交技术检测结果发现,150例患者BCR-ABL融合基因均为阳性,其中费城(Ph)染色体阳性142例(94.67%),阴性8例(5.33%);142例Ph染色体阳性患者中,初诊Ph阳性且伴有额外染色体异常14例(9.86%),变异易位4例(2.82%),标准易位t(9;22)(q34;q11)124例(87.32%)。14例伴有额外染色体异常的患者中,“主要路径”异常8例,-Y异常2例,“次要路径”异常4例。在TKI治疗期间,46例标准易位患者出现额外染色体异常,以染色体数目异常为主,此类患者疾病进展和出现点突变的比例较高(P<0.05)。与标准易位患者比较,初诊CML慢性期伴有额外染色体异常患者无病生存率明显降低(P<0.05),而与总生存率的比较,并无明显差异(P>0.05)。与无额外染色体异常患者比较,CML慢性期TKI治疗期间出现额外染色体异常者无病生存率及总生存率明显下降(P<0.05).

结论: 部分CML患者在疾病发生和发展过程中可出现额外染色体异常,此类患者发生疾病进展的风险性较高.

MeSH terms

  • Chromosome Aberrations
  • Cytogenetic Analysis
  • Cytogenetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Philadelphia Chromosome*
  • Protein Kinase Inhibitors / therapeutic use*
  • Translocation, Genetic


  • Protein Kinase Inhibitors