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

  1. Lookup NU author(s)
  2. Professor Anthony Moorman
  3. Claire Schwab
  4. Hannah Ensor
  5. Dr Lisa Russell
  6. Heather Morrison
  7. Lisa Jones
  8. Dino Masic
  9. Professor Christine Harrison
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
JournalJournal of Clinical Oncology
Year2012
Volume30
Issue25
Pages3100-3108
ISSN (print)0732-183X
ISSN (electronic)1527-7755
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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.
PublisherAmerican Society of Clinical Oncology
URLhttp://dx.doi.org/10.1200/JCO.2011.40.3907
DOI10.1200/JCO.2011.40.3907
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