Adult Low-Hypodiploid Acute B-Lymphoblastic Leukemia With IKZF3 Deletion and TP53 Mutation: Comparison With Pediatric Patients

Am J Clin Pathol. 2015 Aug;144(2):263-70. doi: 10.1309/AJCPW83OXPYKPEEN.

Abstract

Objectives: Chromosomal ploidy is a major risk stratification tool for acute B-cell lymphoblastic leukemia (B-ALL). Low hypodiploidy and near-haploidy are thought to be confined to pediatric B-ALL and associated with a poor prognosis. Doubling of either a low-hypodiploid or a near-haploid clone results in an apparently high-hyperdiploid karyotype, which is often misclassified for risk.

Methods: We studied four patients with B-ALL who had chromosome genomic array testing (CGAT), along with fluorescence in situ hybridization and mutation testing.

Results: We identified a unique case of adult B-ALL with masked low hypodiploidy (mLH) by genomic duplication, along with a somatic deletion of the IKZF3 gene and a somatic TP53 mutation. Three cases of pediatric B-ALL with mLH, two with TP53 mutations and one untested, were also identified and compared with the adult patient.

Conclusions: CGAT was critical in the genotype clarification of these cases through detection of copy-neutral loss of heterozygosity and should be considered performing for B-ALL with apparent hyperdiploidy for accurate prognostic risk stratification and treatment planning.

Keywords: B-cell lymphoblastic leukemia; IKZF; TP53; chromosome genomic array testing; copy-neutral loss of heterozygosity; single-nucleotide polymorphism array.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Humans
  • Ikaros Transcription Factor / genetics*
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Male
  • Middle Aged
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Sequence Deletion
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult

Substances

  • IKZF3 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ikaros Transcription Factor