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IGH@ Translocations, CRLF2 Deregulation and Microdeletions in Adolescents and Adults with Acute Lymphoblastic Leukemia

Lookup NU author(s): Professor Anthony Moorman, Claire Schwab, Hannah Ensor, Dr Lisa Russell, Heather Morrison, Lisa Jones, Dr Dino Masic, Professor Christine Harrison

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Abstract

Purpose To determine the prevalence and prognostic impact of significant (acute lymphoblastic leukemia (ALL)- related genes: CRLF2 deregulation (CRLF2-d), IGH@ translocations (IGH@-t), and deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1 and 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 CRLF2-d [P2RY8-CRLF2 (n=7), IGH@-CRLF2 (n=13)] while 36 (8%) patients harboured an IGH@-t with a different partner gene. There was little overlap between IGH@-t, CRLF2-d and established chromosomal abnormalities. Deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1 or 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 CRLF2-d, IGH@-t and 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 IGH@-t or IKZF1 deletions had a lower OS (27% and 35%). 4 Conclusions CRLF2-d and 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. CRLF2-d, IGH@-t and IKZF1 deletions are associated with poor outcome in adolescent and adult ALL.


Publication metadata

Author(s): 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

Publication type: Article

Journal: Journal of Clinical Oncology

Year: 2012

Volume: 30

Issue: 25

Pages: 3100-3108

Print publication date: 30/06/2012

ISSN (print): 0732-183X

ISSN (electronic): 1527-7755

Publisher: American Society of Clinical Oncology

URL: http://dx.doi.org/10.1200/JCO.2011.40.3907

DOI: 10.1200/JCO.2011.40.3907


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