A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia.
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 abnormal...
| Main Authors: | , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
American Society of Hematology
2014
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| _version_ | 1826283914194321408 |
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| author | Moorman, A Enshaei, A Schwab, C Wade, R Chilton, L Elliott, A Richardson, S Hancock, J Kinsey, SE Mitchell, C Goulden, N Vora, A Harrison, C |
| author_facet | Moorman, A Enshaei, A Schwab, C Wade, R Chilton, L Elliott, A Richardson, S Hancock, J Kinsey, SE Mitchell, C Goulden, N Vora, A Harrison, C |
| author_sort | Moorman, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:05:59Z |
| format | Journal article |
| id | oxford-uuid:8b5b0321-18a6-4e64-ac01-3efccc99faa8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:05:59Z |
| publishDate | 2014 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | oxford-uuid:8b5b0321-18a6-4e64-ac01-3efccc99faa82022-03-26T22:37:32ZA novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8b5b0321-18a6-4e64-ac01-3efccc99faa8EnglishSymplectic Elements at OxfordAmerican Society of Hematology2014Moorman, AEnshaei, ASchwab, CWade, RChilton, LElliott, ARichardson, SHancock, JKinsey, SEMitchell, CGoulden, NVora, AHarrison, CRecent 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. |
| spellingShingle | Moorman, A Enshaei, A Schwab, C Wade, R Chilton, L Elliott, A Richardson, S Hancock, J Kinsey, SE Mitchell, C Goulden, N Vora, A Harrison, C A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title | A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title_full | A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title_fullStr | A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title_full_unstemmed | A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title_short | A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. |
| title_sort | novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia |
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