Abstract:
:Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome.
journal_name
Bloodjournal_title
Bloodauthors
Rand V,Parker H,Russell LJ,Schwab C,Ensor H,Irving J,Jones L,Masic D,Minto L,Morrison H,Ryan S,Robinson H,Sinclair P,Moorman AV,Strefford JC,Harrison CJdoi
10.1182/blood-2011-01-329961subject
Has Abstractpub_date
2011-06-23 00:00:00pages
6848-55issue
25eissn
0006-4971issn
1528-0020pii
blood-2011-01-329961journal_volume
117pub_type
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