Objective: To explore whether the ABL(Δexon7) and ABL(35INS) spliceosome contributed to TKIs resistance.
Methods: Screening ABL(Δexon7) and ABL(35INS) in 74 normal people and 76 CML patients (53 patients in remission and 23 patients with TKIs resistance) by using polyacrylamide gel electrophoresis combined with cloning sequencing.
Results: A novel spliceosome ABL(Δexon7+ 35INS) (ABL(Δexon7) and ABL(3)5INS existed at the same time) was identified and the mutation was detected in 8 (10.8%) of 74 normal people, 4 (7.5%) of 53 remission patients and 2 (8.7%) of 23 resistant patients. While 47 (63.5%) cases expressed ABL(Δexon7) and 8 (10.8% ) cases expressed ABL(35INS) in 74 healthy people, 30 (56.6%) cases expressed ABL(Δexon7) and 5 (9.4% ) cases expressed ABL(35INS) in 53 remission patients, 12 (52.2%) cases expressed ABL(Δexon7) and 3(13.0%) cases expressed ABL(35INS) in 23 resistant patients. Three kinds of spliceosome in all groups had no statistical difference.
Conclusion: ABL(Δexon7+ 35INS), ABL(Δexon7) and ABL(35INS) may be not uncommon in ABL gene and were unrelated to resistance in CML with TKIs treatment. ABL(35INS) were often accompanying with exon 7 deletion.
目的: 探讨ABL基因的剪接体ABLΔexon7和ABL35INS是否与酪氨酸激酶抑制剂（TKI）耐药的发生有关。
方法: 采用聚丙烯酰胺凝胶电泳法结合PCR扩增产物直接测序法，检测74名健康人和76例慢性髓性白血病（CML）患者（TKI治疗有效组53例，耐药组23例）ABLΔexon7和ABL35INS剪接体的发生率。
结果: 发现并鉴定一种新的剪接体ABLΔexon7+35INS（ABLΔexon7和ABL35INS剪接体同时存在），在健康对照组、TKI治疗有效组和耐药组检出率分别为10.8%（8/74）、7.5%（4/53）和8.7%（2/23）。74名健康对照者中47名（63.5%）表达ABLΔexon7剪接体，8名（10.8%）表达ABL35INS剪接体；53例TKI治疗有效的CML患者中30例（56.6%）表达ABLΔexon7剪接体，5例（9.4%）表达ABL35INS剪接体；23例发生耐药的CML患者中12例（52.2%）表达ABLΔexon7剪接体，3例（13.0%）表达ABL35INS剪接体，比较以上各组结果，差异均无统计学意义（P值均>0.05）。
结论: 新剪接体ABLΔexon7+35INS、ABLΔexon7和ABL35INS与TKI治疗发生耐药无关，同时发现ABL35INS剪接体的发生往往会伴随外显子7的缺失。