IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia

Anthony V. Moorman, Claire Schwab, Hannah M. Ensor, Lisa J. Russell, Heather Morrison, Lisa Jones, Dino Masic, Bella Patel, Jacob M. Rowe, Martin Tallman, Anthony H. Goldstone, Adele K. Fielding, Christine J. Harrison

Research output: Contribution to journalArticle

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 and Methods: The cohort comprised 454 patients (age 15 to 60 years old) treated on the multicenter United Kingdom Acute Lymphoblastic Leukaemia Trial XII/Eastern Cooperative Oncology Group 2993 trial (UKALLXII/ECOG2993) with Philadelphia-negative B-cell precursor ALL. Fluorescent in situ hybridization and multiplex ligation-dependent probe amplification were used to detect these genetic alterations. Results: Twenty patients (5%) had CRLF2-d (P2RY8-CRLF2, n = 7; IGH@-CRLF2, n = 13), and 36 patients (8%) harbored 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 (33%) of 304 patients harboring one and 102 (33%) harboring two or more alterations, occurring with varying frequency in all cytogenetic subgroups. The 5-year event-free survival, relapse-free survival (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 with other patients (30%), whereas those with IGH@-t or IKZF1 deletions had a lower OS (27% and 35%, respectively). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)3100-3108
Number of pages9
JournalJournal of Clinical Oncology
Volume30
Issue number25
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Moorman, A. V., Schwab, C., Ensor, H. M., Russell, L. J., Morrison, H., Jones, L., Masic, D., Patel, B., Rowe, J. M., Tallman, M., Goldstone, A. H., Fielding, A. K., & Harrison, C. J. (2012). IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. Journal of Clinical Oncology, 30(25), 3100-3108. https://doi.org/10.1200/JCO.2011.40.3907