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Deregulation and Microdeletions in Adolescents and Adults with Acute Lymphoblastic Leukemia
Lookup NU author(s)
Professor Anthony Moorman
Dr Lisa Russell
Professor Christine Harrison
Moorman AV, Schwab C, Ensor HM, Russell LJ, Morrison H, Jones L, Masic D, Patel B, Rowe JM, Tallman M, Goldstone AH, Fielding AK, Harrison CJ
Journal of Clinical Oncology
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Purpose To determine the prevalence and prognostic impact of significant (acute lymphoblastic leukemia (ALL)- related genes:
CRLF2 deregulation (
IGH@ translocations (
IGH@-t), and deletions of
EBF1, in adolescents and adults.
Patients/Methods The cohort comprised 454 patients (15-60 years old) treated on UKALLXII/ECOG2993 with Philadelphia-negative B-cell precursor ALL. Fluorescence in situ hybridisation (FISH) and Multiplex Ligation-dependent Probe Amplification (MLPA) were used to detect these genetic alterations.
Results Twenty (5%) patients had
IGH@-CRLF2 (n=13)] while 36 (8%) patients harboured an
IGH@-t with a different partner gene. There was little overlap between
CRLF2-d and established chromosomal abnormalities. Deletions of
EBF1 were prevalent with 101/304 (33%) cases harbouring one and 102 (33%) two or more alterations, occurring with varying frequency in all cytogenetic subgroups. The 5 year event-free, relapse-free (RFS) and overall survival (OS) rates for the whole cohort were 40%, 55% and 43%, respectively. Patients with
IKZF1 deletions were associated with an inferior outcome in univariate but not multivariate analysis. In particular,
CRLF2-d patients had a lower RFS compared to other patients (30%), whereas those with
IKZF1 deletions had a lower OS (27% and 35%). 4
IGH@-t represent distinct subtypes of adolescent and adult ALL. Deletions of key B-cell differentiation and cell cycle control genes are highly prevalent but vary in frequency by cytogenetic subgroup.
IKZF1 deletions are associated with poor outcome in adolescent and adult ALL.
American Society of Clinical Oncology
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