Molecular monitoring of residual disease using antigen receptor genes in childhood acute lymphoblastic leukaemia

Abstract

Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are assumed to be unique ‘fingerprint-like’ sequences for each acute lymphoblastic leukaemia (ALL). Various clonal Ig/TCR gene rearrangements can be identified at diagnosis in virtually all childhood ALL patients, representing molecular targets for detection of minimal residual disease (MRD) during follow-up analysis. The usage of at least two MRD-PCR targets per patient generally ensures high sensitivity (⩽1:104 normal cells) and prevents false-negative results owing to ongoing or secondary rearrangements.MRD monitoring in childhood ALL employing Ig/TCR gene rearrangements as PCR targets has significant prognostic value. This is particularly powerful for evaluation of early treatment response and consequently can be used for improved therapy stratification. Prolonged continuous MRD monitoring might be important for patients at intermediate or high risk of relapse. MRD monitoring in second complete remission identifies patients with excellent drug sensitivity and predicts outcome after stem cell transplantation.