PURPOSE: The 9p21 locus, encoding three important @entity5 suppressors ( @entity986 / @entity986 , @entity986 /ARF, and @entity9288 / @entity9288 ), is a major target of inactivation in the pathogenesis of many @entity1 @entity5 . @entity1 AND METHODS: To explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive @entity981 ( @entity981 ) and to investigate their prognostic value, 112 @entity1 (101 de novo and 11 relapsed cases) were analyzed by genome-wide single-nucleotide polymorphism arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases. RESULTS: @entity986 and @entity9288 genomic alterations were identified in 29% and 25% of newly diagnosed @entity1 , respectively. Deletions were monoallelic in 72% of cases, and in 43% of them, the minimal overlapping region of the lost area spanned only the @entity4640 gene locus. An analysis conducted at relapse showed an increase in the detection rate of @entity986 /ARF loss (47%) compared with the time of diagnosis (P = 0.06). Point mutations within the 9p21 locus were found at very low levels, with only a nonsynonymous substitution in the exon 2 of @entity986 . Of note, deletions of @entity4640 were significantly associated with poor outcomes in terms of overall survival (P = 0.0206), disease free-survival (P = 0.0010), and cumulative incidence of relapse (P = 0.0014). CONCLUSIONS: Inactivation of the 9p21 locus by genomic deletion is a frequent event in BCR-ABL1-positive @entity981 . Deletions are frequently acquired during @entity1778 progression and are a poor prognostic marker of long-term outcomes.

XXXX alterations impair prognosis in adult BCR-ABL1-positive @entity981 @entity1 .

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'PATIENTS'] @entity981 :: ('MESH:D054198', 'Disease') :: ['ALL', 'acute lymphoblastic leukemia'] @entity986 :: ('1029', 'Gene') :: ['CDKN2A/ARF', 'CDKN2A', 'p16', 'p14'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity9288 :: ('1030', 'Gene') :: ['CDKN2B', 'p15'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity4640 :: ('1029;1030', 'Gene') :: ['CDKN2A/B']
@entity4640 :: (1029;1030,Gene) :: ['CDKN2A/B']
