Nylund S J, Ruutu T, Saarinen U, Knuutila S
Department of Medical Genetics, University of Helsinki, Finland.
Br J Haematol. 1994 Dec;88(4):778-83. doi: 10.1111/j.1365-2141.1994.tb05117.x.
Metaphase DNA fluorescence in situ hybridization (metaphase-FISH) was performed on follow-up samples from 60 patients suffering from haemopoietic malignancies (acute and chronic myeloid leukaemia, acute lymphoblastic leukaemia, non-Hodgkin's lymphoma and myelodysplastic syndrome). All patients had clonal chromosomal trisomies or translocations at diagnosis, and were treated by bone marrow transplantation (BMT), chemotherapy (CT) or interferon-alpha therapy. Metaphase-FISH was performed during therapy-induced complete haematological remission (CR) (BMT and CT patients) using biotin-labelled whole chromosome paint probes. 28% of all patients in CR were shown by FISH to have abnormal metaphase cells, and 62% of this group suffered a clinical relapse. Of those with negative FISH results (72%), 12% relapsed. In three CML patients treated with BMT a small population of t(9;22)-positive cells was demonstrated. These cells disappeared during follow-up without causing a relapse. One ALL patient had abnormal cells a short time after start of therapy but was also later found FISH-negative. Furthermore, we demonstrated that metaphase-FISH is a suitable method for quantifying the proportion of abnormal cells in CML patients during interferon-alpha therapy. Metaphase-FISH was also employed to detect a local relapse in an ALL patient. Thus, metaphase-FISH was found reliable and sensitive for detection of minimal residual disease in patients with haemopoietic malignancies.
对60例造血系统恶性肿瘤（急性和慢性髓性白血病、急性淋巴细胞白血病、非霍奇金淋巴瘤和骨髓增生异常综合征）患者的随访样本进行中期DNA荧光原位杂交（中期-FISH）检测。所有患者在诊断时均有克隆性染色体三体或易位，并接受了骨髓移植（BMT）、化疗（CT）或α干扰素治疗。对于治疗诱导的完全血液学缓解（CR）期（BMT和CT患者）的患者，使用生物素标记的全染色体涂染探针进行中期-FISH检测。FISH检测显示，所有处于CR期的患者中有28%存在中期细胞异常，该组中有62%的患者出现临床复发。FISH结果为阴性的患者（72%）中，有12%复发。在3例接受BMT治疗的慢性粒细胞白血病患者中，发现了一小部分t(9;22)阳性细胞。这些细胞在随访期间消失，未导致复发。1例急性淋巴细胞白血病患者在治疗开始后短时间内出现异常细胞，但后来FISH检测也为阴性。此外，我们证明中期-FISH是一种适用于量化慢性粒细胞白血病患者在α干扰素治疗期间异常细胞比例的方法。中期-FISH还用于检测1例急性淋巴细胞白血病患者的局部复发。因此，发现中期-FISH在检测造血系统恶性肿瘤患者的微小残留病方面可靠且敏感。
