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Título
ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial
Autor(es)
Materia
Mutación
supervivencia
Leucemia linfocítica crónica
ensayo clínico
Clasificación UNESCO
2410.02 Anatomía Humana
Fecha de publicación
2014
Editor
Sociedad Argentina de Hematología
Citación
Matthew, J.J., Rose-Zerilli, J.F., Parker, H., Parker, A., Rodríguez, A.E., Chaplin, T., Gardiner, A., Steele, A.J., Collins, A., Young, B.D., Skowronska, A., Catovsky, D., Stankovic, T., Oscier, D.G., Strefford, J.C. (2013). ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. Haematologica, 99 (4) pp 736-742. https://doi.org/10.3324/haematol.2013.098574
Resumen
[EN] ATM mutation and BIRC3 deletion and/or mutation have independently been shown to have prognostic significance
in chronic lymphocytic leukemia. However, the relative clinical importance of these abnormalities in
patients with a deletion of 11q encompassing the ATM gene has not been established. We screened a cohort of
166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion and mutation and determined the
overall and progression-free survival among the 133 of these cases treated within the UK LRF CLL4 trial. SNP6.0
profiling demonstrated that BIRC3 deletion occurred in 83% of 11q-deleted cases and always co-existed with ATM
deletion. For the first time we have demonstrated that 40% of BIRC3-deleted cases have concomitant deletion and
mutation of ATM. While BIRC3 mutations were rare, they exclusively occurred with BIRC3 deletion and a wildtype
residual ATM allele. In 11q-deleted cases, we confirmed that ATM mutation was associated with a reduced
overall and progression-free survival comparable to that seen with TP53 abnormalities, whereas BIRC3 deletion
and/or mutation had no impact on overall and progression-free survival. In conclusion, in 11q-deleted patients
treated with first-line chemotherapy, ATM mutation rather than BIRC3 deletion and/or mutation identifies a subgroup
with a poorer outcome.
URI
ISSN
0390-6078
DOI
10.3324/haematol.2013.098574
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