Published online before print March 26, 2009

This Article Full Text Full Text (PDF) All Versions of this Article: jmoldx.2009.080047v1 11/3/194    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brisco, M. J. Articles by Morley, A. A. Search for Related Content PubMed PubMed Citation Articles by Brisco, M. J. Articles by Morley, A. A.

Journal of Molecular Diagnostics 2009, Vol. 11, No. 3
Copyright © 2009 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2009.080047

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

Michael J. Brisco^*, Sue Latham^*, Rosemary Sutton, Elizabeth Hughes^*, Vicki Wilczek^*, Katrina van Zanten^*, Bradley Budgen^*, Anita Y. Bahar, Maria Malec, Pamela J. Sykes^*, Bryone J. Kuss^*, Keith Waters, Nicola C. Venn, Jodie E. Giles, Michelle Haber, Murray D. Norris, Glenn M. Marshall and Alexander A. Morley^*

From the Department of Hematology and Genetic Pathology, * Flinders University and Medical Centre, Adelaide; the Children’s Cancer Institute Australia for Medical Research, University of New South Wales, Sydney; the Department of Clinical Hematology and Oncology, Royal Children’s Hospital, Victoria; and the Centre for Children’s Cancer and Blood Disorders, Sydney Children’s Hospital, Sydney, Australia

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.

This article has been cited by other articles:

				A. A. Morley, S. Latham, M. J. Brisco, P. J. Sykes, R. Sutton, E. Hughes, V. Wilczek, B. Budgen, K. van Zanten, B. J. Kuss, et al. Sensitive and Specific Measurement of Minimal Residual Disease in Acute Lymphoblastic Leukemia J. Mol. Diagn., May 1, 2009; 11(3): 201 - 210. [Abstract] [Full Text] [PDF]