Pediatric T-Cell Lymphoblastic Leukemia and T-Cell Lymphoblastic Lymphoma: Differences in the Common Deleted Region and the Prognostic Impact of Chromosome 6q Deletions.

Abstract

Background/Objectives: Deletions of chromosome 6q have been reported in a variety of hematological malignancies. Regarding their prognostic impact, however, the data are inconclusive, as most of the published studies included different subtypes, different immunophenotypes and/or differently treated patients (pts).Therefore our analyses focused on 109 pediatric pts with T-cell lymphoblastic-lymphoma (T-LBL) compared with 127 pediatric pts with T-cell lymphoblastic leukemia (T-ALL). Both groups were treated uniformly according to the BFM-ALL-type treatment strategy.Design/Methods: Deletions of chromosome 6q were examined by loss-of-heterozygosity (LOH) analysis of 25 microsatellite-markers located on chromosome 6q14-q24. DNA samples were amplified by PCR, followed by fragment-length analysis on a genetic analyzer.Results: Between 03/95-06/04 a total of 217 pediatric T-LBL pts were registered at the NHL-BFM study center and treated uniformly with ALL-type treatment strategy. 109 T-LBL pts were evaluable for LOH analysis, including 21 out of 27 pts who suffered relapse. In the 109 pts a total of 1,688 markers were analyzed successfully. Patterns of LOH were detectable in 22 pts. Analysis of the putative deleted regions revealed LOH of all informative markers in 5 pts and interstitial deletions in 17 cases. A common deleted region of 13 cases was flanked by markers D6S1682 and D6S1716 at band 6q16. There were no statistically significant differences in LOH-positive versus LOH-negative T-LBL pts with respect to age, sex ratio, stage, BM or CNS involvement. However, detection of LOH at 6q14-24 was associated with poor outcome: Probability of disease-free-survival (DFS) was 91±3% for LOH-negative versus 38±11% for LOH-positive pts (p<0.0001).In comparison, a total of 186 T-ALL pts were consecutively registered in the trial ALL-BFM 2000 between 08/99-06/02. Of these, 127 pts were evaluable for LOH analysis, including 22 out of 27 pts with relapse. In the 127 pts a total of 3,109 markers were analyzed successfully. Patterns of LOH were detected in 16 pts with proximal interstitial deletions in 15 out of the 16 cases. The 4.3 Mb common deleted region was flanked by markers D6S1627 and D6S1644. There were no significant differences between LOH-positive versus LOH-negative pts neither in clinical characteristics nor in treatment response or outcome.Conclusions: The pattern of 6q-deletions as well as the prognostic impact differ between pediatric T-LBL and T-ALL. LOH at 6q is detectable in 20% of pediatric T-LBL compared with 13% of pediatric T-ALL. In T-ALL the common deleted region is localized in chromosomal band 6q14. LOH is not associated with clinical parameters or outcome. In T-LBL the most frequently deleted marker is localized in band 6q16 and detectable LOH is associated with poor outcome. A prospective analysis of a larger series of pts is necessary to confirm the prognostic value of 6q deletions in T-LBL.