Characterization of the ETO and AML1-ETO proteins involved in the 8;21 translocation in acute myelogenous leukemia

Xiao Feng Le, David Claxton, Steve Kornblau, You Hong Fan, Zhao Mei Mu, Kun Sang Chang

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Abstract

The AML1 and ETO genes are disrupted by the nonrandom chromosomal translocation t(8;21) in acute myelogenous leukemia (AML). While the AML1 gene encodes a transcription factor indispensable for definitive hematopoiesis, the biological function of ETO is unknown. To understand the role of ETO and AML1-ETO in the pathogenesis of AML, the full length cDNAs of ETO and AML1-ETO were cloned and antibodies against AML1 and ETO proteins have been developed in our laboratory. Western blot analysis showed that ETO and AML1-ETO were identified as 70 kDa and 94 kDa proteins, respectively, and that both proteins, like AML1, were associated with the nuclear matrix. To examine whether the t(8;21)-positive AMLs expressed a 94-kDa AML1-ETO, protein fractions isolated from leukemia blasts of 10 patients with t(8;21)- positive AML and the Kasumi-1 cells were analyzed by Western blotting. The 94 kDa AML1-ETO fusion protein was detected in all samples. However, this fusion protein was not detectable in all 40 patients with t(8;21)-negative AMLs. The biological significance of AML1-ETO was examined in K562 cells, which stably overexpress AML1-ETO. We found that AML1-ETO blocked the erythroid differentiation of K562 cells induced by low doses of Ara-C. Thus, t(8;21)- positive AMLs appear to overexpress the AML1-ETO fusion protein, which may be responsible for differentiation block and leukemogenesis in AML.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalEuropean Journal of Haematology
Volume60
Issue number4
StatePublished - May 5 1998

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Acute Myeloid Leukemia
Proteins
K562 Cells
Western Blotting
Nuclear Matrix
Genetic Translocation
Cytarabine
Hematopoiesis
Genes
Leukemia
Transcription Factors
Complementary DNA
Antibodies

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Le, Xiao Feng ; Claxton, David ; Kornblau, Steve ; Fan, You Hong ; Mu, Zhao Mei ; Chang, Kun Sang. / Characterization of the ETO and AML1-ETO proteins involved in the 8;21 translocation in acute myelogenous leukemia. In: European Journal of Haematology. 1998 ; Vol. 60, No. 4. pp. 217-225.
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abstract = "The AML1 and ETO genes are disrupted by the nonrandom chromosomal translocation t(8;21) in acute myelogenous leukemia (AML). While the AML1 gene encodes a transcription factor indispensable for definitive hematopoiesis, the biological function of ETO is unknown. To understand the role of ETO and AML1-ETO in the pathogenesis of AML, the full length cDNAs of ETO and AML1-ETO were cloned and antibodies against AML1 and ETO proteins have been developed in our laboratory. Western blot analysis showed that ETO and AML1-ETO were identified as 70 kDa and 94 kDa proteins, respectively, and that both proteins, like AML1, were associated with the nuclear matrix. To examine whether the t(8;21)-positive AMLs expressed a 94-kDa AML1-ETO, protein fractions isolated from leukemia blasts of 10 patients with t(8;21)- positive AML and the Kasumi-1 cells were analyzed by Western blotting. The 94 kDa AML1-ETO fusion protein was detected in all samples. However, this fusion protein was not detectable in all 40 patients with t(8;21)-negative AMLs. The biological significance of AML1-ETO was examined in K562 cells, which stably overexpress AML1-ETO. We found that AML1-ETO blocked the erythroid differentiation of K562 cells induced by low doses of Ara-C. Thus, t(8;21)- positive AMLs appear to overexpress the AML1-ETO fusion protein, which may be responsible for differentiation block and leukemogenesis in AML.",
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Characterization of the ETO and AML1-ETO proteins involved in the 8;21 translocation in acute myelogenous leukemia. / Le, Xiao Feng; Claxton, David; Kornblau, Steve; Fan, You Hong; Mu, Zhao Mei; Chang, Kun Sang.

In: European Journal of Haematology, Vol. 60, No. 4, 05.05.1998, p. 217-225.

Research output: Contribution to journalArticle

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AU - Le, Xiao Feng

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AU - Chang, Kun Sang

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