IGH and IGK gene rearrangements as PCR targets for pediatric Burkitt's lymphoma and mature B-ALL MRD analysis.
We recently reported that minimal residual disease (MRD) and minimal disseminated disease (MDD), assessed by long-distance PCR (LD-PCR) for t(8;14), are negative prognostic factors in mature B-cell acute lymphoblastic leukemia (B-ALL) and in Burkitt's lymphoma (BL). However, t(8;14) is detectable in only about 70% of patients, thus preventing MRD studies by this approach in the remaining patients. At present, no molecular assays have been reported for MRD and MDD analysis in t(8;14)-negative patients. The aim of our study was to evaluate the characteristics of patient-specific immunoglobulin (Ig) gene rearrangements as RQ-PCR targets for MRD analysis, in order to extend MRD studies to those patients who are not eligible for the LD-PCR assay. The study was performed according to the guidelines of the European Study Group on MRD detection in ALL (ESG-MRD-ALL). Overall, 36 B-ALL and 19 BL cases were analyzed. Multiple PCR reactions were performed for each sample to identify heavy and kappa light-chain rearrangements. A total of 97 RQ-PCR targets (62 for B-ALL, 35 for BL) were analyzed for sensitivity. The rearrangement pattern identified was similar to that reported for normal peripheral blood lymphocytes. In 88% of the targets, a sensitivity of at least 10(-4) was achieved. In 87% of patients (84% of B-ALLs, 95% of BLs) at least one sensitive target was available. All PCR targets identified at diagnosis were preserved at relapse. Our results suggest that MDD and MRD can be successfully studied using a single sensitive Ig target in the great majority of B-ALL and BL cases. The combination of LD-PCR and Ig-based assays will allow MRD analysis in virtually all of the patients.
Lovisa
Federica
F
Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, Padua, Italy.
Mussolin
Lara
L
Corral
Lilia
L
Pillon
Marta
M
Cazzaniga
Giovanni
G
Biondi
Andrea
A
Rosolen
Angelo
A
D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000235:genetics*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains