慢性髓性白血病一种新剪接体ABL^△exon7＋35INS

Discovery of a novel spliceosome of ABL gene （ABL^△exon7＋35INS） and its association with TKIs resistance in chronic myeloid leukemia

目的探讨ABL基因的剪接体ABL^△exon7和ABL^35INS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）ABL^△exon7和ABL^35LNS剪接体的发生率。结果发现并鉴定一种新的剪接体ABL^△exon7＋35INS（ABL^△exon7和ABL^35INS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ABL^△exon7剪接体，8名（10．8％）表达ABLINS剪接体；53例TKI治疗有效的CML患者中30例（56．6％）表达ABL“””剪接体，5例（9．4％）表达ABL””剪接体；23例发生耐药的CML患者中12例（52．2％）表达ABL^△exon7剪接体，3例（13．0％）表达ABLINS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ABL^△exon7＋35INS和ABL^35INS与TKI治疗发生耐药无关，同时发现ABL^35INS剪接体的发生往往会伴随外显子7的缺失。

Objective To explore whether the ^△exon7 and ABL^35INS spliceosome contributed to TKIs resistance. Methods ScreeningABL^△exon7 and ABL^35LNSin 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~~x~~7＋35~s （ABL^△exon7 and ABL^35LNSexisted 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 ^△exon7 and 8 （10.8%） eases expressed ABL35rNs in 74 healthy people, 30 （56.6%） cases expressed ^△exon7 and 5 （9.4%） cases expressed ABL35INs in 53 remission patients, 12 （52.2%） cases expressed ABLa^x^7 and 3 （13.0%） cases expressed ABL351Ns in 23 resistant patients. Three kinds of spliceosome in all groups had no statistical difference. Conclusion ABL△exon7 ＋ 35INs, ABL^xexon7 and ABL35rNs may be not uncommon in ABL gene and were unrelated to resistance in CML with TKIs treatment. ABL^35LNS were often accompanying with exon 7 deletion.