AML1-FOG2 fusion protein in myelodysplasia

Edward M. Chan; Elisha M. Comer; Frank C. Brown; Kathleen E. Richkind; Melissa L. Holmes; Beng H. Chong; Roger Shiffman; Dong Er Zhang; Marilyn L. Slovak; Cheryl L. Willman; Constance T. Noguchi; Yanjun Li; Devan J. Heiber; Lori Kwan; Rebecca J. Chan; Gail H. Vance; Heather C. Ramsey; Robert A. Hromas

doi:10.1182/blood-2004-07-2762

AML1-FOG2 fusion protein in myelodysplasia

Edward M. Chan, Elisha M. Comer, Frank C. Brown, Kathleen E. Richkind, Melissa L. Holmes, Beng H. Chong, Roger Shiffman, Dong Er Zhang, Marilyn L. Slovak, Cheryl L. Willman, Constance T. Noguchi, Yanjun Li, Devan J. Heiber, Lori Kwan, Rebecca J. Chan, Gail H. Vance, Heather C. Ramsey, Robert A. Hromas

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia.

Original language	English (US)
Pages (from-to)	4523-4526
Number of pages	4
Journal	Blood
Volume	105
Issue number	11
DOIs	https://doi.org/10.1182/blood-2004-07-2762
State	Published - Jun 1 2005
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Chan, E. M., Comer, E. M., Brown, F. C., Richkind, K. E., Holmes, M. L., Chong, B. H., Shiffman, R., Zhang, D. E., Slovak, M. L., Willman, C. L., Noguchi, C. T., Li, Y., Heiber, D. J., Kwan, L., Chan, R. J., Vance, G. H., Ramsey, H. C., & Hromas, R. A. (2005). AML1-FOG2 fusion protein in myelodysplasia. Blood, 105(11), 4523-4526. https://doi.org/10.1182/blood-2004-07-2762

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title = "AML1-FOG2 fusion protein in myelodysplasia",

abstract = "Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia.",

author = "Chan, {Edward M.} and Comer, {Elisha M.} and Brown, {Frank C.} and Richkind, {Kathleen E.} and Holmes, {Melissa L.} and Chong, {Beng H.} and Roger Shiffman and Zhang, {Dong Er} and Slovak, {Marilyn L.} and Willman, {Cheryl L.} and Noguchi, {Constance T.} and Yanjun Li and Heiber, {Devan J.} and Lori Kwan and Chan, {Rebecca J.} and Vance, {Gail H.} and Ramsey, {Heather C.} and Hromas, {Robert A.}",

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doi = "10.1182/blood-2004-07-2762",

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AU - Chan, Edward M.

AU - Comer, Elisha M.

AU - Brown, Frank C.

AU - Richkind, Kathleen E.

AU - Holmes, Melissa L.

AU - Chong, Beng H.

AU - Shiffman, Roger

AU - Zhang, Dong Er

AU - Slovak, Marilyn L.

AU - Willman, Cheryl L.

AU - Noguchi, Constance T.

AU - Li, Yanjun

AU - Heiber, Devan J.

AU - Kwan, Lori

AU - Chan, Rebecca J.

AU - Vance, Gail H.

AU - Ramsey, Heather C.

AU - Hromas, Robert A.

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia.

AB - Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia.

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AML1-FOG2 fusion protein in myelodysplasia

Abstract

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