TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse.
Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene rearrangements were detected in 35% of childhood (n=161) and adult (n=172) precursor-B-ALL patients (Vbeta-(Dbeta)-Jbeta in 25%; Dbeta-Jbeta in 15%). The presence of TCRB rearrangements showed a significant relation with age (highest frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1 transcripts, and was associated with relatively high frequencies of IGK-Kde, TCRG, and Vdelta2-Jalpha rearrangements. In 62 out of 65 patients with Southern blot-detected Vbeta-(Dbeta)-Jbeta and/or Dbeta-Jbeta rearrangements, at least one TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20 out of 24 (83%) Vbeta-(Dbeta)-Jbeta rearrangements and eight out of 14 (57%) Dbeta-Jbeta rearrangements remained stable. Using real-time quantitative PCR, a quantitative range < or =10(-4) was obtained in 64% of TCRB gene rearrangements and in 86% of cases a sensitivity < or =10(-4) was obtained. In conclusion, TCRB gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively stable and sensitive PCR targets for detection of minimal residual disease, particularly if this concerns complete Vbeta-(Dbeta)-Jbeta rearrangements.
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
V H J
VH
van der Velden
M
M
Brüggemann
P G
PG
Hoogeveen
M
M
de Bie
P G
PG
Hart
T
T
Raff
H
H
Pfeifer
S
S
Lüschen
T
T
Szczepański
E R
ER
van Wering
M
M
Kneba
J J M
JJ
van Dongen
D000328:Adult; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein