Portal de Periódicos da CAPES

A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia

2014; Elsevier BV; Volume: 124; Issue: 9 Linguagem: Inglês

10.1182/blood-2014-03-562918

1528-0020

Anthony V. Moorman, Amir Enshaei, Claire Schwab, Rachel Wade, Lucy Chilton, Alannah Elliott, Stacey Richardson, Jeremy Hancock, Sally E. Kinsey, Christopher Mitchell, Nicholas Goulden, Ajay Vora, Christine J. Harrison,

Acute Myeloid Leukemia Research

Recent genomic studies have provided a refined genetic map of acute lymphoblastic leukemia (ALL) and increased the number of potential prognostic markers. Therefore, we integrated copy-number alteration data from the 8 most commonly deleted genes, subordinately, with established chromosomal abnormalities to derive a 2-tier genetic classification. The classification was developed using 809 ALL97/99 patients and validated using 742 United Kingdom (UK)ALL2003 patients. Good-risk (GR) genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy-number status for all 8 genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk (PR). Three-quarters of UKALL2003 patients had a GR genetic profile and a significantly improved event-free survival (EFS) (94%) compared with patients with a PR genetic profile (79%). This difference was driven by a lower relapse rate (4% vs 17%), was seen across all patient subgroups, and was independent of other risk factors. Even genetic GR patients with minimal residual disease (>0.01%) at day 29 had an EFS in excess of 90%. In conclusion, the integration of genomic and cytogenetic data defines 2 subgroups with distinct responses to treatment and identifies a large subset of children suitable for treatment deintensification.