Abnormalities of Chromosome Bands 13q12 to 13q14 in Childhood Acute Lymphoblastic Leukemia

Author:

Heerema Nyla A.1,Sather Harland N.1,Sensel Martha G.1,Lee Mei K.1,Hutchinson Raymond J.1,Nachman James B.1,Reaman Gregory H.1,Lange Beverly J.1,Steinherz Peter G.1,Bostrom Bruce C.1,Gaynon Paul S.1,Uckun Fatih M.1

Affiliation:

1. From the Department of Genetics, Parker Hughes Institute; Children’s Cancer Group ALL Biology Reference Laboratory and Parker Hughes Institute, St Paul; Division of Hematology-Oncology, Children’s Hospitals and Clinics, Minneapolis, MN; Group Operations Center, Children’s Cancer Group, Arcadia; Department of Preventive Medicine, University of Southern California; Department of Pediatric Hematology-Oncology, Children’s Hospital, Los Angeles, CA; Department of Pediatrics, Hematology-Oncology, University of...

Abstract

PURPOSE: Little is known about nonrandom deletions of chromosome bands 13q12 to 13q14 (13q12–14) in acute lymphoblastic leukemia (ALL). We determined the prognostic significance of cytogenetically identified breakpoints in 13q12–14 in children with newly diagnosed ALL treated on Children’s Cancer Group protocols from 1988 to 1995. PATIENTS AND METHODS: Breakpoints in 13q12–14 were identified in 36 (2%) of the 1,946 cases with accepted cytogenetic data. Outcome analysis used standard life-table methods. RESULTS: Seventeen patients (47%) with an abnormal 13q12–14 were classified, according to the National Cancer Institute (NCI), as poor risk, and 15 patients (42%) were standard risk; four (11%) were infants less than 12 months of age. Eight cases had balanced rearrangements of 13q12–14, 27 patients had a partial loss of 13q, and one had both a partial gain and a partial loss. The most frequent additional abnormalities among these patients were an abnormal 12p, a del(6q), a del(9p), a 14q11 breakpoint, and an 11q23 breakpoint. Nineteen patients were pseudodiploid, 10 were hyperdiploid, and seven were hypodiploid. Patients with an abnormal 13q12–14 had significantly worse event-free survival than patients lacking such an abnormality, with estimates at 6 years of 61% (SD = 14%) and 74% (SD = 1%), respectively (P = .04; relative risk = 1.74). Overall survival, however, was similar for the two groups (P = .25). The prognostic effect of an abnormal 13q was attenuated in a multivariate analysis adjusted for NCI risk status and ploidy (P = .72). CONCLUSION: Aberrations of 13q12–14 may contribute to leukemogenesis of childhood ALL and confer increased risk of treatment failure but are associated with other poor-risk features.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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