The use of monoclonal gene rearrangement for detection of minimal residual disease in acute lymphoblastic leukemia of childhood

Sensitive quantification of minimal residual disease (MRD) using the polymerase chain reaction (PCR) is strongly predictive of outcome in childhood acute lymphoblastic leukemia (ALL), with MRD levels at the end of induction therapy of >10(-3) predicting a poor outcome. Methods for sensitive quant...

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Bibliographic Details
Published in:	Leukemia Vol. 11; no. 1; pp. 153 - 158
Main Authors:	SYKES, P. J, SNELL, L. E, BRISCOL, M. J, NEOH, S.-H, HUGHES, E, DOLMAN, G, PENG, L.-M, BENNETT, A, TOOGOOD, I, MORLEY, A. A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 1997
Subjects:	Biological and medical sciences Child Gene Rearrangement, B-Lymphocyte, Heavy Chain - genetics Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor - genetics Hematology Humans Investigative techniques, diagnostic techniques (general aspects) Medical sciences Neoplasm, Residual Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Polymerase Chain Reaction - methods Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Sensitivity and Specificity Human Heavy peptide chain Immunoglobulins Gamma-Peptide chain T cell receptor Acute Minimal residual disease Malignant hemopathy Polymerase chain reaction Gene Lymphoproliferative syndrome T-Lymphocyte Gene rearrangement Diagnosis Acute lymphocytic leukemia Molecular biology Child Monoclonal immunoglobulin
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Summary:	Sensitive quantification of minimal residual disease (MRD) using the polymerase chain reaction (PCR) is strongly predictive of outcome in childhood acute lymphoblastic leukemia (ALL), with MRD levels at the end of induction therapy of >10(-3) predicting a poor outcome. Methods for sensitive quantification are, however, complicated and time-consuming. Detection by PCR of monoclonal immunoglobulin heavy chain (IgH) and T cell receptor (TCR) gene rearrangements is simple and can be used in routine laboratories but is non-quantitative and of lower but uncertain sensitivity. The aim of this study was to determine the value of detection of monoclonality in identification of different levels of MRD. We looked for monoclonality in 64 bone marrow aspirates which had been obtained from 31 patients with B lineage ALL at various times during induction therapy and for which levels of MRD had been determined by limiting dilution analysis using patient-specific PCR primers. Detection of monoclonality identified levels of MRD of > or =10(-3) during induction with a sensitivity of 78% and a specificity of 93%. The positive and negative predictive values were 0.86 and 0.88, respectively. The sensitivity of detection of a monoclonal IgH rearrangement was greater than that for the TCRgamma locus during induction as an IgH rearrangement was detected more often than a TCRgamma rearrangement in patients who had both IgH and TCRgamma rearrangement at diagnosis. Detection of monoclonality is therefore a simple and quick test applicable to the majority of patients with ALL and it may be useful in identifying high-risk patients at the end of induction and in identifying relapsing patients later during therapy.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0887-6924 1476-5551
DOI:	10.1038/sj.leu.2400542