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 detectab...

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Veröffentlicht in:Laboratory investigation 2009-10, Vol.89 (10), p.1182-1186
Hauptverfasser: Lovisa, Federica, Mussolin, Lara, Corral, Lilia, Pillon, Marta, Cazzaniga, Giovanni, Biondi, Andrea, Rosolen, Angelo
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Sprache:eng
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Zusammenfassung: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.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.2009.81