Tobal K, Johnson P R, Saunders M J, Harrison C J, Liu Yin J A
University Department of Haematology, Manchester Royal Infirmary.
Br J Haematol. 1995 Sep;91(1):104-8. doi: 10.1111/j.1365-2141.1995.tb05253.x.
The pericentric inversion of chromosome 16 [inv(16)(p13q22)] and t(16;16)(p13;q22) are chromosomal rearrangements frequently associated with AML FAB type M4Eo resulting in the production of a fusion gene CBFB/MYH11. We studied 17 patients with a chromosome 16 abnormality (eight M4Eo, two M1, one M2, three M4 without abnormal eosinophils, three MDS) for the presence of CBFB/MYH11 transcripts using an RT-PCR technique. 10 AML patients with inv(16) tested RT-PCR positive (eight at presentation, one in remission, one in remission and relapse). Three of these patients were originally reported by cytogenetic analysis to have del(16q22) but the positive RT-PCR results prompted a cytogenetic re-examination, resulting in the correction of the reports to inv(16). We show that although inv(16) is closely associated with AML M4Eo, it can also be detected in cases of AML M4 without abnormal eosinophils. Three cases of MDS with inv(16) were also RT-PCR positive. Four patients with other chromosome 16 abnormalities were RT-PCR negative. Four AML patients with inv(16) were studied in remission. All were RT-PCR positive, including one patient in remission for 108 months and one 22 months post allogeneic bone marrow transplant. In the latter two remission patients, RT-PCR evaluation was positive in bone marrow (BM) but not in peripheral blood, suggesting that BM may be the more informative. We conclude that this technique is valuable in the accurate molecular classification of AML, particularly as treatment options may be influenced by such information. Though RT-PCR is highly sensitive in detecting CBFB/MYH11 fusion transcripts during remission, monitoring of minimal residual disease in patients with inv(16) remains to be established.
16号染色体的臂间倒位[inv(16)(p13q22)]和t(16;16)(p13;q22)是常与急性髓系白血病FAB M4Eo型相关的染色体重排，会导致融合基因CBFB/MYH11的产生。我们使用逆转录聚合酶链反应（RT-PCR）技术研究了17例有16号染色体异常的患者（8例M4Eo、2例M1、1例M2、3例无异常嗜酸性粒细胞的M4、3例骨髓增生异常综合征），以检测CBFB/MYH11转录本的存在情况。10例有inv(16)的急性髓系白血病患者RT-PCR检测呈阳性（8例初诊时阳性，1例缓解期阳性，1例缓解期及复发期阳性）。其中3例患者最初经细胞遗传学分析报告为del(16q22)，但RT-PCR阳性结果促使进行细胞遗传学重新检查，结果将报告更正为inv(16)。我们发现，虽然inv(16)与急性髓系白血病M4Eo密切相关，但在无异常嗜酸性粒细胞的急性髓系白血病M4病例中也可检测到。3例有inv(16)的骨髓增生异常综合征病例RT-PCR也呈阳性。4例有其他16号染色体异常的患者RT-PCR呈阴性。研究了4例缓解期有inv(16)的急性髓系白血病患者。所有患者RT-PCR均呈阳性，包括1例缓解108个月的患者和1例异基因骨髓移植后22个月的患者。在后两例缓解期患者中，RT-PCR评估在骨髓中呈阳性，但在外周血中呈阴性，提示骨髓可能提供更多信息。我们得出结论，该技术在急性髓系白血病的准确分子分类中很有价值，特别是因为治疗方案可能会受此类信息影响。虽然RT-PCR在检测缓解期的CBFB/MYH11融合转录本方面高度敏感，但inv(16)患者微小残留病的监测仍有待确立。
