Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia: Analysis by means of array-based comparative genomic hybridization

Shinobu Tsuzuki, Sivasundaram Karnan, Keizo Horibe, Kimikazu Matsumoto, Koji Kato, Takeshi Inukai, Kumiko Goi, Kanji Sugita, Shinpei Nakazawa, Yumiko Kasugai, Ryuzo Ueda, Masao Seto

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

The TEL (ETV6)-AML1 (RUNX1) chimeric gene fusion is the most common genetic abnormality in childhood acute lymphoblastic leukemias. Evidence suggests that this chimeric gene fusion constitutes an initiating mutation that is necessary but insufficient for the development of leukemia. In a search for additional genetic events that could be linked to the development of leukemia, we applied a genome-wide array-comparative genomic hybridization technique to 24 TEL-AML1 leukemia samples and two cell lines. It was found that at least two chromosomal imbalances were involved in all samples. Recurrent regions of chromosomal imbalance (>10% of cases) and representative involved genes were gain of chromosomes 10 (17%) and 21q (25% RUNX1) and loss of 12p13.2 (87% TEL), 9p21.3 (29% p16INK4a/ARF), 9p13.2 (25% PAX5), 12q21.3 (25% BTG1), 3p21 (21%; LIMD1), 6q21 (17%; AIM1 and BLIMP1), 4q31.23 (17%; NR3C2), 11q22-q23 (13%; ATM) and 19q13.11-q13.12 (13%; PDCD5). Enforced expression of TEL and to a lesser extent BTG1, both single genes known to be located in their respective minimum common region of loss, inhibited proliferation of the TEL-AML1 cell line Reh. Together, these findings suggest that some of the genes identified as lost by array-comparative genomic hybridization may partly account for the development of leukemia.

Original languageEnglish
Pages (from-to)698-706
Number of pages9
JournalCancer Science
Volume98
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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