IGH@ translocations are prevalent in teenagers and young adults with acute lymphoblastic leukemia and are associated with a poor outcome.
OBJECTIVE
To determine the prevalence and prognostic association of immunoglobulin heavy chain (IGH@) translocations in acute lymphoblastic leukemia (ALL).


METHODS
The cohort comprised 3,269 patients treated on either the UKALL2003 trial for children and adolescents (1 to 24 years old) or the UKALLXII trial for adolescents and adults (15 to 59 years old). High-throughput fluorescent in situ hybridization was used to detect IGH@ translocations.


RESULTS
We identified IGH@ translocations in 5% of patients with ALL (159 of 3,269 patients), in patients with both B-cell (148 of 2,863 patients) and T-cell (11 of 408 patients) disease. Multiple partner genes were identified including CRLF2 (n = 35), five members of the CEPB gene family (n = 17), and ID4 (n = 11). The level of the IGH@-positive clone varied and indicated that some IGH@ translocations were primary events, whereas others were secondary aberrations often associated with other established aberrations. The age profile of patients with IGH@ translocations was distinctive, with a median age of 16 years and peak incidence of 11% among 20- to 24-year-old patients. Among patients with B-cell precursor ALL who were Philadelphia chromosome negative, those with an IGH@ translocation had an inferior overall survival compared with other patients (UKALL2003: hazard ratio, 2.37; 95% CI, 1.34 to 4.18; P = .003; UKALLXII: hazard ratio, 1.73; 95% CI, 1.22 to 2.47; P = .002). However, this adverse effect was not independent of age or minimal residual disease status and did not seem to be driven by an increased risk of relapse.


CONCLUSIONS
IGH@ translocations define a genetic feature that is frequent among adolescents and young adults with ALL. Although associated with an adverse outcome in adults, it is not an independent prognostic factor in children and adolescents.
Lisa J. Russell, Amir Enshaei, Lisa Jones, Amy Erhorn, Dino Masic, Helen Bentley, Anthony V. Moorman, and Christine J. Harrison, Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne; Karl S. Laczko, Leica Microsystems, Gateshead; Adele K. Fielding, Royal Free and University College London Medical School; Anthony H. Goldstone, University College London Hospital; Nicholas Goulden, Great Ormond St Hospital, London; Christopher D. Mitchell, John Radcliffe Hospital; Rachel Wade, Clinical Trial Service Unit, University of Oxford, Oxford; and Ajay Vora, Sheffield Children's Hospital, Sheffield, United Kingdom.
Lisa J
LJ
Russell
Amir
A
Enshaei
Lisa
L
Jones
Amy
A
Erhorn
Dino
D
Masic
Helen
H
Bentley
Karl S
KS
Laczko
Adele K
AK
Fielding
Anthony H
AH
Goldstone
Nicholas
N
Goulden
Christopher D
CD
Mitchell
Rachel
R
Wade
Ajay
A
Vora
Anthony V
AV
Moorman
Christine J
CJ
Harrison
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D014178:Translocation, Genetic; D055815:Young Adult
D007143:Immunoglobulin Heavy Chains