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149例B细胞慢性淋巴细胞白血病中通过荧光原位杂交检测到的IGH@重排的遗传和免疫表型特征

Genetic and immunophenotypic profile of IGH@ rearrangement detected by fluorescence in situ hybridization in 149 cases of B-cell chronic lymphocytic leukemia.

作者信息

Lu Gary, Kong Yue, Yue Changjun

机构信息

Department of Hematopathology, Box 350, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.

出版信息

Cancer Genet Cytogenet. 2010 Jan 1;196(1):56-63. doi: 10.1016/j.cancergencyto.2009.08.021.

Abstract

Recent studies have shown a higher frequency of immunoglobulin heavy (IGH@) locus rearrangement in B-cell chronic lymphocytic leukemia (B-CLL) than previously reported. However, association of the IGH@ rearrangement with specific chromosomal abnormalities and immunophenotypic markers in B-CLL is still under further investigation. In this study, we analyzed 149 bone marrow aspirate or peripheral blood specimens from patients diagnosed with B-CLL, evaluated by four different laboratory studies: morphology examination, three- or four-color flow cytometry analysis, conventional cytogenetics, and fluorescence in situ hybridization (FISH) with a dual-color, break-apart IGH@ probe in addition to a B-CLL FISH probe panel for del(11)(q22) ATM, del(13)(q14.3), del(17)(p13) TP53, and +12. An IGH@ rearrangement was found by FISH in 24 cases (16.0%). Of these 24 cases, 16 (67%) contained chromosomal abnormalities, including t(14;19)(q32;q13.2), t(8;14)(q24;q32), and t(14;18)(q32;q21). In addition, a cryptic deletion of the immunoglobulin heavy variable region (IGHV) was revealed. Using 30% as the cutoff for positive CD38 expression, 22 of the 24 cases (92%) were positive for CD38. The present results further confirm that IGH@ rearrangement is not a rare genomic abnormality in B-CLL, and also show both that t(14;19)(q32;q13.2) is the most common cytogenetic change involving IGH@ rearrangement detected by FISH in B-CLL and that IGH@ rearrangement is correlated with CD38 expression. It is appropriate to include an IGH@ probe in the FISH panel for B-CLL diagnosis.

摘要

近期研究表明,与此前报道相比,B细胞慢性淋巴细胞白血病(B-CLL)中免疫球蛋白重链(IGH@)基因座重排的频率更高。然而,IGH@重排在B-CLL中与特定染色体异常及免疫表型标志物之间的关联仍在进一步研究中。在本研究中,我们分析了149例经诊断为B-CLL患者的骨髓穿刺液或外周血标本,通过四项不同的实验室研究进行评估:形态学检查、三色或四色流式细胞术分析、传统细胞遗传学以及荧光原位杂交(FISH),其中除了用于检测del(11)(q22) ATM、del(13)(q14.3)、del(17)(p13) TP53和+12的B-CLL FISH探针组合外,还使用了双色、断裂分离IGH@探针。通过FISH在24例(16.0%)中发现了IGH@重排。在这24例中,16例(67%)存在染色体异常,包括t(14;19)(q32;q13.2)、t(8;14)(q24;q32)和t(14;18)(q32;q21)。此外,还发现了免疫球蛋白重链可变区(IGHV)的隐匿性缺失。以CD38表达阳性的截断值为30%,24例中的22例(92%)CD38呈阳性。目前的结果进一步证实IGH@重排在B-CLL中并非罕见的基因组异常,同时还表明t(14;19)(q32;q13.2)是通过FISH在B-CLL中检测到的涉及IGH@重排的最常见细胞遗传学改变,且IGH@重排与CD38表达相关。在用于B-CLL诊断的FISH检测组合中加入IGH@探针是合适的。

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