Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia.
OBJECTIVE
Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are excellent patient-specific targets for polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). Nevertheless, instability of these targets during the course of the disease has important implications for PCR-based MRD monitoring and may lead to false negative results.


METHODS
Several studies have shown that Ig and TCR targets are reasonably stable in ALL between diagnosis and first relapse, but up to now, there are no data on the stability of these targets between first and second relapse. We, therefore, performed a PCR-study on bone marrow samples from 49 children with precursor B-ALL at first and second relapse. Homo-heteroduplex PCR analyses were used for identification of clonal IGH, IGK-Kde, TCRG and TCRD gene rearrangements. Clonal targets were studied by sequencing and/or comparative homo-heteroduplex analysis.


RESULTS
In 52% (25/48) of the patients, all PCR targets identified at first relapse were preserved at second relapse; in 92% (44/48) of the patients at least one target and in 73% (35/48) at least two targets remained stable. Best stability was found for IGH and TCRG gene rearrangements.


CONCLUSIONS
Based on these first data about clonal stability of Ig and TCR targets between first and second relapse of childhood precursor B-ALL, we developed a stepwise strategy for appropriate selection of stable PCR targets for MRD monitoring. This strategy was applicable in 84% of the relapsed patients and resulted in at least one stable MRD-PCR target per patient in 98% of these children.
Guggemos
Andreas
A
Charité Medical Centre, Campus Virchow-Klinikum, Department of Pediatric Oncology and Hematology, Augustenburger Platz 1, 13353 Berlin, Germany.
Eckert
Cornelia
C
Szczepanski
Tomasz
T
Hanel
Claudia
C
Taube
Tillmann
T
van der Velden
Vincent H J
VH
Graf-Einsiedel
Hagen
H
Henze
Günter
G
Seeger
Karlheinz
K
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D019143:Evolution, Molecular; D005787:Gene Frequency; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000473:pathology