急性髓系白血病中免疫球蛋白及T细胞受体β和γ基因的构型：40例分析中的陷阱

Configuration of immunoglobulin and T cell receptor beta and gamma genes in acute myeloid leukaemia: pitfalls in the analysis of 40 cases.

作者信息

Parreira L, Carvalho C, Moura H, Melo A, Santos P, Guimarães J E, Parreira A

机构信息

Instituto de Histologia e Embriologia da Faculdade de Medicina Lisboa, Portugal.

出版信息

J Clin Pathol. 1992 Mar;45(3):193-200. doi: 10.1136/jcp.45.3.193.

DOI:10.1136/jcp.45.3.193

PMID:1372916

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC495467/

Abstract

AIMS

To evaluate the overall incidence of immunoglobulin (Ig) and T cell receptor (TCR) beta and gamma gene rearrangements in a series of 40 cases of acute myeloid leukaemia (AML) and to determine whether structural modifications of these genes could be correlated with the abnormal expression of lymphoid markers in malignant cells.

METHODS

All cases were classified according to the criteria of the FAB group and immunophenotyped with a panel of monoclonal antibodies reactive with myeloid and lymphoid differentiation antigens. DNA analysis was performed by the method of Southern using probes for the Ig JH, TCR-C beta 1, and TCR-J tau 1 regions.

RESULTS

Phenotypic analysis showed that in addition to myeloid markers, 10 cases expressed lymphoid antigens: CD7 in seven (of which three were TdT positive, one CD2 positive, and one CD19 positive) and CD19 in three. Southern blot analysis showed that bands with sizes different from the germ line control were present in the TCR beta genes in 11 cases: in six of 30 with pure myeloid phenotype and in five of 10 of those expressing lymphoid markers. A close observation of the size and patterns of those bands, however, showed that they could be artefactual. Indeed, further analysis showed that they were either due to resistant Eco RI/Hind III sites at the beta locus or to plasmid contamination. Rearranged genes were eventually found in only two of the 40 cases: at the Ig JH region in one of the 30 with pure myeloid phenotype (3.3%) and at the TCR gamma genes in one of 10 with lymphoid markers (10%).

CONCLUSIONS

These observations showed that Ig/TCR gene rearrangements were rare in this AML series (overall incidence of 5%) and that they were not significantly more common in cases with aberrant expression of lymphoid markers. The size and pattern of the potential non-germline bands that can be found in these loci must be carefully evaluated.

摘要

目的

评估40例急性髓系白血病（AML）中免疫球蛋白（Ig）以及T细胞受体（TCR）β和γ基因重排的总体发生率，并确定这些基因的结构修饰是否与恶性细胞中淋巴样标志物的异常表达相关。

方法

所有病例均按照FAB组标准分类，并用一组与髓系和淋巴系分化抗原反应的单克隆抗体进行免疫表型分析。采用Southern印迹法，使用针对Ig JH、TCR-Cβ1和TCR-Jτ1区域的探针进行DNA分析。

结果

表型分析显示，除髓系标志物外，10例表达淋巴样抗原：7例表达CD7（其中3例TdT阳性，1例CD2阳性，1例CD19阳性），3例表达CD19。Southern印迹分析显示，11例TCRβ基因中出现了与种系对照大小不同的条带：30例纯髓系表型中有6例，10例表达淋巴样标志物的病例中有5例。然而，对这些条带的大小和模式进行仔细观察发现，它们可能是人为造成的。实际上，进一步分析表明，它们要么是由于β位点的Eco RI/Hind III抗性位点，要么是由于质粒污染。最终在40例病例中仅发现2例基因重排：30例纯髓系表型中有1例在Ig JH区域（3.3%），10例有淋巴样标志物的病例中有1例在TCRγ基因（10%）。