Chromosome 6q deletion in precursor T-cell lymphoblastic lymphoma and leukemia of childhood and adolescence

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BurkhardtBirgit-2007-02-16.pdf (759.2 KB)

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2006

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DOI:
http://dx.doi.org/10.22029/jlupub-13137

Abstract

Precursor T lymphoblastic lymphoma (T-LBL) is the second most common subtype of Non-Hodgkin Lymphoma (NHL) in children and adolescents. Favorable survival rates have been achieved with current combination chemotherapy regimens; however failure of frontline treatment is still fatal for the majority of patients. Currently there are no strong prognostic criteria known that would allow the minority of patients at risk of failure to be identified early enough to expose them to a more intense or new therapy. Cytogenetic data from four index patients from clinical trial NHL-BFM 95 exhibited a common deleted region at chromosomal band 6q15-q16. Interestingly, all four patients suffered from a relapse. In the literature, chromosome 6q deletions have been reported for various hematological malignancies, but the prognostic impact is still inconclusive. In the present study the frequency of chromosome 6q deletions in T-LBL, the common deleted region and the prognostic impact was analyzed. Secondly, identical analyses were performed in pediatric precursor T leukemia (T-ALL) patients as T-LBL and T-ALL are considered to be biologically closely related. Both groups were treated uniformly according to an ALL-BFM-type treatment strategy. 6q deletions were examined by loss-of-heterozygosity analysis (LOH) of 25 microsatellite markers on chromosome 6q14-q24. A total of 1,671 markers were successfully analyzed from 108 T-LBL patients. LOH was detectable in 21 patients. Markers D6S1682 and D6S468 flanked a chromosomal region which was affected by deletion in 13 cases. The cumulative incidence of relapse was 9±3% for LOH negative versus 63±12% for LOH positive patients (P < 0.001). In comparison, a total of 3,109 markers were successfully analyzed from 127 T-ALL patients. LOH was detected in 16 patients, with proximal interstitial deletions in 15 cases. Markers D6S1627 and D6S1644 flanked the 4.3-Mb common deleted region. LOH at 6q was not associated with outcome. Thus, we conclude that LOH on chromosome 6q14-q24 was associated with a high risk of relapse in children with T-LBL and that the pattern of 6q deletions and the prognostic impact differed between pediatric T-LBL and T-ALL. These results might indicate differences in the biology of the cells in pediatric T-LBL and T-ALL.

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