c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells

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c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. / Hess, JL; Bittner, CB; Zeisig, DT; Bach, C; Fuchs, U; Borkhardt, A; Frampton, Jonathan; Slany, RK.

In: Blood, Vol. 108, No. 1, 01.07.2006, p. 297-304.

Research output: Contribution to journalArticle

Harvard

Hess, JL, Bittner, CB, Zeisig, DT, Bach, C, Fuchs, U, Borkhardt, A, Frampton, J & Slany, RK 2006, 'c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells', Blood, vol. 108, no. 1, pp. 297-304. https://doi.org/10.1182/blood-2005-12-5014

APA

Hess, JL., Bittner, CB., Zeisig, DT., Bach, C., Fuchs, U., Borkhardt, A., Frampton, J., & Slany, RK. (2006). c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. Blood, 108(1), 297-304. https://doi.org/10.1182/blood-2005-12-5014

Vancouver

Hess JL, Bittner CB, Zeisig DT, Bach C, Fuchs U, Borkhardt A et al. c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. Blood. 2006 Jul 1;108(1):297-304. https://doi.org/10.1182/blood-2005-12-5014

Author

Hess, JL ; Bittner, CB ; Zeisig, DT ; Bach, C ; Fuchs, U ; Borkhardt, A ; Frampton, Jonathan ; Slany, RK. / c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. In: Blood. 2006 ; Vol. 108, No. 1. pp. 297-304.

Bibtex

@article{a77dde6d21c24872a0036b81e36b135b,
title = "c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells",
abstract = "Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.",
author = "JL Hess and CB Bittner and DT Zeisig and C Bach and U Fuchs and A Borkhardt and Jonathan Frampton and RK Slany",
year = "2006",
month = jul,
day = "1",
doi = "10.1182/blood-2005-12-5014",
language = "English",
volume = "108",
pages = "297--304",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

RIS

TY - JOUR

T1 - c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells

AU - Hess, JL

AU - Bittner, CB

AU - Zeisig, DT

AU - Bach, C

AU - Fuchs, U

AU - Borkhardt, A

AU - Frampton, Jonathan

AU - Slany, RK

PY - 2006/7/1

Y1 - 2006/7/1

N2 - Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.

AB - Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.

U2 - 10.1182/blood-2005-12-5014

DO - 10.1182/blood-2005-12-5014

M3 - Article

C2 - 16507773

VL - 108

SP - 297

EP - 304

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -