Amplification of AML1 in acute lymphoblastic leukemia is associated with a poor outcome

Robinson, H.M., Broadfield, Z.J., Cheung, K.L., Harewood, L., Harris, R.L., Jalali, G.R., Martineau, M., Moorman, A.V., Taylor, K.E., Richards, S., Mitchell, C. and Harrison, C.J. (2003) Amplification of AML1 in acute lymphoblastic leukemia is associated with a poor outcome. Leukemia, 17 (11), 2249-2250. (doi:10.1038/sj.leu.2403081).

Abstract

A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL (~70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 TCRB TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients.

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