Determining the Repertoire of IGH Gene Rearrangements to Develop Molecular Markers for Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia

被引:7
|
作者
Brisco, Michael J. [1 ,2 ]
Latham, Sue [1 ,2 ]
Sutton, Rosemary [3 ]
Hughes, Elizabeth [1 ,2 ]
Wilczek, Vicki [1 ,2 ]
van Zanten, Katrina [1 ,2 ]
Budgen, Bradley [1 ,2 ]
Bahar, Anita Y. [3 ]
Malec, Maria [3 ]
Sykes, Pamela J. [1 ,2 ]
Kuss, Bryone J. [1 ,2 ]
Waters, Keith
Venn, Nicola C. [3 ]
Giles, Jodie E. [3 ]
Haber, Michelle [3 ]
Norris, Murray D. [3 ]
Marshall, Glenn M. [4 ]
Morley, Alexander A. [1 ,2 ]
机构
[1] Flinders Univ S Australia, Dept Hematol & Genet Pathol, Adelaide, SA, Australia
[2] Med Ctr, Adelaide, SA, Australia
[3] Univ New S Wales, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia
[4] Sydney Childrens Hosp, Ctr Childrens Canc & Blood Disorders, Sydney, NSW, Australia
来源
JOURNAL OF MOLECULAR DIAGNOSTICS | 2009年 / 11卷 / 03期
基金
英国医学研究理事会;
关键词
TIME QUANTITATIVE PCR; CLONAL IMMUNOGLOBULIN; CONCERTED ACTION; HEAVY-CHAIN; CHILDHOOD; RELAPSE; CHILDREN; QUANTIFICATION; INDUCTION; PROTOCOLS;
D O I
10.2353/jmoldx.2009.080047
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Molecular markers for minimal residual disease in B-lineage acute lymphoblastic leukemia were identified by determining, at the time of diagnosis, the repertoire of rearrangements of the immunoglobulin heavy chain (IGH) gene using segment-specific variable (V), diversity (D), and junctional (J) primers in two different studies that involved a total study population of 75 children and 18 adults. This strategy, termed repertoire analysis, was compared with the conventional strategy of identifying markers using family-specific V, D, and J primers for a variety of antigen receptor genes. Repertoire analysis detected significantly more markers for the major leukemic clone than did the conventional strategy, and one or more IgH rearrangements that were suitable for monitoring the major clone were detected in 96% of children and 94% of adults. Repertoire analysis also detected significantly more IGH markers for minor clones. Some minor clones were quite large and a proportion of them would not be able to be detected by a minimal residual disease test directed to the marker for the major clone. IGH repertoire analysis at diagnosis has potential advantages for the identification of molecular markers for the quantification of minimal residual disease in acute lymphoblastic leukemia cases. An IGH marker enables very sensitive quantification of the major leukemic clone, and the detection of minor clones may enable early identification of additional patients who are prone to relapse. (J mol Diagn 2009, 11:194-200; DOI: 10.2353/jmoldx.2009.080047)
引用
收藏
页码:194 / 200
页数:7
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