Rigolin G M, Bigoni R, Milani R, Cavazzini F, Roberti M G, Bardi A, Agostini P, Della Porta M, Tieghi A, Piva N, Cuneo A, Castoldi G
Section of Hematology, Department of Biomedical Sciences, University of Ferrara, Corso Giovecca, 203, 44100 Ferrara, Italy.
Leukemia. 2001 Dec;15(12):1841-7. doi: 10.1038/sj.leu.2402293.
At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situ hybridization (FISH) is more sensitive than CCA allowing for the detection of minor clones and of submicroscopic lesions. We have analyzed by FISH 101 MDS patients with normal karyotype for the occurrence of the abnormalities which are most frequently observed in MDS (ie -5/5q-, -7/7q-, +8, 17p-). In 18 patients, 15 to 32% of interphase cells were found to carry one FISH abnormality. Six patients presented trisomy 8, five had del(5)(q31), five del(7)(q31), one monosomy 7 and one del(17)(p13). FISH abnormalities were more frequently observed among patients with an increased percentage of bone marrow blasts (P = 0.001). FISH abnormalities were also associated with a higher rate of progression into AML (13/18 vs 12/83, P < 0.001) and were predictive for a worse prognosis (P < 0.001). Multivariate analysis indicated that FISH positivity and IPSS risk group were independent predictors for a poor survival (P = 0.0057 and 0.0123, respectively) and for leukemic transformation (P = 0.0006 and 0.035, respectively). Leukemic transformation in FISH-positive patients was associated in all cases with an expansion of the abnormal clone. Our data demonstrated that a significant proportion of MDS patients with normal karyotype presented, if analyzed by FISH, clones of cytogenetically abnormal cells which played a determinant role in the progression of the disease. The presence of FISH abnormalities identified a group of MDS patients with normal karyotype characterized by an inferior prognosis.
在诊断时，通过传统细胞遗传学分析（CCA），约一半的骨髓增生异常综合征（MDS）患者呈现正常核型。荧光原位杂交（FISH）比CCA更敏感，能够检测到微小克隆和亚微观病变。我们通过FISH分析了101例核型正常的MDS患者，以检测MDS中最常观察到的异常情况（即-5/5q-、-7/7q-、+8、17p-）。在18例患者中，发现15%至32%的间期细胞携带一种FISH异常。6例患者出现8号染色体三体，5例有del(5)(q31)，5例del(7)(q31)，1例7号染色体单体和1例del(17)(p13)。FISH异常在骨髓原始细胞百分比增加的患者中更常见（P = 0.001）。FISH异常还与进展为急性髓系白血病（AML）的更高发生率相关（13/18 vs 12/83，P < 0.001），并预示预后较差（P < 0.001）。多变量分析表明，FISH阳性和国际预后评分系统（IPSS）风险组是生存不良（分别为P = 0.0057和0.0123）以及白血病转化（分别为P = 0.0006和0.035）的独立预测因素。FISH阳性患者的白血病转化在所有病例中均与异常克隆的扩增相关。我们的数据表明，如果通过FISH分析，相当一部分核型正常的MDS患者存在细胞遗传学异常细胞克隆，这些克隆在疾病进展中起决定性作用。FISH异常的存在确定了一组核型正常但预后较差的MDS患者。
