Cuneo A, Bigoni R, Negrini M, Bullrich F, Veronese M L, Roberti M G, Bardi A, Rigolin G M, Cavazzini P, Croce C M, Castoldi G
Dipartimento di Scienze Biomediche e Terapie Avanzate, Universita di Ferrara, Italy.
Cancer Res. 1997 Mar 15;57(6):1144-50.
Conventional chromosome analysis (CCA) and fluorescent in situ hybridization (FISH) studies, using a 390-kb yeast artificial chromosome probe spanning the area of multiple breakpoints of the BCL1 locus at 11q13, were performed on 57 patients fulfilling the French-American-British criteria for the diagnosis of atypical B-cell chronic lymphocytic leukemia (CLL). To better define the incidence of 13q deletions and trisomy 12, FISH analysis was also performed using a cosmid probe that recognized a DNA sequence between the Rb gene and the D13S25 locus at band 13q14 and a chromosome 12-specific pericentromeric probe. All patients were characterized by cytoimmunological and hematological studies. Fourteen cases displayed three fluorescent signals in 41-98% interphase cells when hybridized to the BCL1 yeast artificial chromosome probe, documenting the presence of BCL1 translocation (BCL1-positive cases). The presence of t(11;14)(q13;q32) was ascertained in 12 cases using CCA and by dual color interphase FISH using the BCLI probe and a 14q telomere probe in 2 karyotypically normal cases. The remaining 43 cases had two signals in more than 95% interphase cells (BCL1-negative) and did not have the t(11;14) at CCA. Although 13q14 deletions were seen by means of CCA in only 5 of 14 BCL1-positive cases, hemizygous or homozygous deletions at band 13q14 were detected by FISH in 11 of 14 BCL1-positive cases, as compared with 17 of 43 BCL1-negative cases (P = 0.01). A subclone with trisomy 12 in addition to BCL1 translocation and del(13q14) was present in four BCL1-positive cases. We arrived at the following conclusions: (a) FISH with this BCL1 YAC probe is an efficient method for the detection of the t(11;14) and of the corresponding involvement of the BCL1 locus in this lymphoproliferative disorder; (b) the majority of BCL1-positive atypical CLLs by French-American-British criteria may carry 13q14 deletions; (c) the recognition of this cytogenetic subset of atypical CLL, sharing some immunological and cytogenetic features with mantle cell lymphoma, may be important, because these patients usually present isolated peripheral blood and marrow lymphocytosis, with or without mild to moderate spleen involvement, and may require early cytotoxic treatment.
对57例符合法国-美国-英国（FAB）非典型B细胞慢性淋巴细胞白血病（CLL）诊断标准的患者进行了常规染色体分析（CCA）和荧光原位杂交（FISH）研究，使用一个跨度为390 kb的酵母人工染色体探针，该探针覆盖11q13上BCL1基因座多个断点区域。为了更好地确定13q缺失和12号染色体三体的发生率，还使用了一种黏粒探针进行FISH分析，该探针可识别位于13q14带的Rb基因和D13S25基因座之间的DNA序列，以及一个12号染色体特异性着丝粒探针。所有患者均通过细胞免疫和血液学研究进行了特征分析。当与BCL1酵母人工染色体探针杂交时，14例患者在41%-98%的间期细胞中显示出三个荧光信号，证明存在BCL1易位（BCL1阳性病例）。使用CCA在12例患者中确定了t(11;14)(q13;q32)的存在，在2例核型正常的病例中，通过使用BCL1探针和14q端粒探针的双色间期FISH也确定了该易位。其余43例患者在超过95%的间期细胞中显示两个信号（BCL1阴性），且在CCA中未发现t(11;14)。尽管在14例BCL1阳性病例中，仅通过CCA在5例中发现了13q14缺失，但通过FISH在14例BCL1阳性病例中的11例中检测到了13q14带的半合子或纯合子缺失，而在43例BCL1阴性病例中有17例检测到（P = 0.01）。4例BCL1阳性病例除了存在BCL1易位和del(13q14)外，还存在12号染色体三体的亚克隆。我们得出以下结论：（a）使用该BCL1酵母人工染色体探针进行FISH是检测t(11;14)以及该淋巴增殖性疾病中BCL1基因座相应受累情况的有效方法；（b）按照FAB标准，大多数BCL1阳性的非典型CLL可能携带13q14缺失；（c）识别这种非典型CLL的细胞遗传学亚组很重要，因为它与套细胞淋巴瘤有一些免疫和细胞遗传学特征相同，这些患者通常仅表现为外周血和骨髓淋巴细胞增多，有或无轻度至中度脾脏受累，可能需要早期细胞毒性治疗。
