TY - JOUR
T1 - Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia
T2 - Analysis by means of array-based comparative genomic hybridization
AU - Tsuzuki, Shinobu
AU - Karnan, Sivasundaram
AU - Horibe, Keizo
AU - Matsumoto, Kimikazu
AU - Kato, Koji
AU - Inukai, Takeshi
AU - Goi, Kumiko
AU - Sugita, Kanji
AU - Nakazawa, Shinpei
AU - Kasugai, Yumiko
AU - Ueda, Ryuzo
AU - Seto, Masao
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1349-7006.2007.00443.x
DO - 10.1111/j.1349-7006.2007.00443.x
M3 - Article
C2 - 17374122
AN - SCOPUS:34147153999
VL - 98
SP - 698
EP - 706
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 5
ER -