IGH@ Translocations Are Prevalent in Teenagers and Young Adults With Acute Lymphoblastic Leukemia and Are Associated With a Poor Outcome
| Autor: | Helen Bentley, Nicholas Goulden, Anthony H. Goldstone, Dino Masic, Karl S. Laczko, Amy Erhorn, Rachel Wade, Amir Enshaei, Adele K. Fielding, Lisa J. Russell, Chris Mitchell, Anthony V. Moorman, Ajay Vora, Christine J. Harrison, Lisa Jones |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Adolescent Lymphoblastic Leukemia Clone (cell biology) Chromosomal translocation Kaplan-Meier Estimate Disease Translocation Genetic Young Adult Internal medicine Humans Medicine Young adult Child In Situ Hybridization Fluorescence Proportional Hazards Models Clinical Trials as Topic business.industry Proportional hazards model Infant Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis Oncology Child Preschool Immunology Cohort Immunoglobulin heavy chain Female Immunoglobulin Heavy Chains business Multiplex Polymerase Chain Reaction |
| Zdroj: | Journal of Clinical Oncology. 32:1453-1462 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2013.51.3242 |
| Popis: | Purpose To determine the prevalence and prognostic association of immunoglobulin heavy chain (IGH@) translocations in acute lymphoblastic leukemia (ALL). Patients and 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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