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Runx1 is essential at two stages of early murine B-cell development

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Runx1 is essential at two stages of early murine B-cell development. / Niebuhr, Birte; Kriebitzsch, Neele; Fischer, Meike; Behrens, Kira; Günther, Thomas; Alawi, Malik; Bergholz, Ulla; Müller, Ursula; Roscher, Susanne; Ziegler, Marion; Buchholz, Frank; Grundhoff, Adam; Stocking, Carol.

in: BLOOD, Jahrgang 122, Nr. 3, 18.07.2013, S. 413-23.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Niebuhr, B, Kriebitzsch, N, Fischer, M, Behrens, K, Günther, T, Alawi, M, Bergholz, U, Müller, U, Roscher, S, Ziegler, M, Buchholz, F, Grundhoff, A & Stocking, C 2013, 'Runx1 is essential at two stages of early murine B-cell development', BLOOD, Jg. 122, Nr. 3, S. 413-23. https://doi.org/10.1182/blood-2013-01-480244

APA

Niebuhr, B., Kriebitzsch, N., Fischer, M., Behrens, K., Günther, T., Alawi, M., Bergholz, U., Müller, U., Roscher, S., Ziegler, M., Buchholz, F., Grundhoff, A., & Stocking, C. (2013). Runx1 is essential at two stages of early murine B-cell development. BLOOD, 122(3), 413-23. https://doi.org/10.1182/blood-2013-01-480244

Vancouver

Niebuhr B, Kriebitzsch N, Fischer M, Behrens K, Günther T, Alawi M et al. Runx1 is essential at two stages of early murine B-cell development. BLOOD. 2013 Jul 18;122(3):413-23. https://doi.org/10.1182/blood-2013-01-480244

Bibtex

@article{4c3c1a4ffe7a4c53856df9421f05e2e7,
title = "Runx1 is essential at two stages of early murine B-cell development",
abstract = "The t(12;21) chromosomal translocation, targeting the gene encoding the RUNX1 transcription factor, is observed in 25% of pediatric acute lymphoblastic leukemia (ALL) and is an initiating event in the disease. To elucidate the mechanism by which RUNX1 disruption initiates leukemogenesis, we investigated its normal role in murine B-cell development. This study revealed 2 critical functions of Runx1: (1) to promote survival and development of progenitors specified to the B-cell lineage, a function that can be substituted by ectopic Bcl2 expression, and (2) to enable the developmental transition through the pre-B stage triggered by the pre-B-cell antigen receptor (pre-BCR). Gene expression analysis and genomewide Runx1 occupancy studies support the hypothesis that Runx1 reinforces the transcription factor network governing early B-cell survival and development and specifically regulates genes encoding members of the Lyn kinase subfamily (key integrators of interleukin-7 and pre-BCR signaling) and the stage-specific transcription factors SpiB and Aiolos (critical downstream effectors of pre-BCR signaling). Interrogation of expression databases of 257 ALL samples demonstrated the specific down-regulation of the SPIB and IKZF3 genes (the latter encoding AIOLOS) in t(12;21) ALL, providing novel insight into the mechanism by which the translocation blocks B-cell development and promotes leukemia.",
keywords = "Animals, Apoptosis, B-Lymphocytes, Binding Sites, Cell Differentiation, Cell Lineage, Cell Proliferation, Cell Survival, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, Core Binding Factor Alpha 2 Subunit, Enhancer Elements, Genetic, Gene Deletion, Gene Expression Regulation, Developmental, Gene Expression Regulation, Leukemic, Gene Targeting, Genome, Humans, Mice, Mice, Inbred C57BL, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Protein Binding, Proto-Oncogene Proteins c-bcl-2, Trans-Activators, Translocation, Genetic",
author = "Birte Niebuhr and Neele Kriebitzsch and Meike Fischer and Kira Behrens and Thomas G{\"u}nther and Malik Alawi and Ulla Bergholz and Ursula M{\"u}ller and Susanne Roscher and Marion Ziegler and Frank Buchholz and Adam Grundhoff and Carol Stocking",
year = "2013",
month = jul,
day = "18",
doi = "10.1182/blood-2013-01-480244",
language = "English",
volume = "122",
pages = "413--23",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

RIS

TY - JOUR

T1 - Runx1 is essential at two stages of early murine B-cell development

AU - Niebuhr, Birte

AU - Kriebitzsch, Neele

AU - Fischer, Meike

AU - Behrens, Kira

AU - Günther, Thomas

AU - Alawi, Malik

AU - Bergholz, Ulla

AU - Müller, Ursula

AU - Roscher, Susanne

AU - Ziegler, Marion

AU - Buchholz, Frank

AU - Grundhoff, Adam

AU - Stocking, Carol

PY - 2013/7/18

Y1 - 2013/7/18

N2 - The t(12;21) chromosomal translocation, targeting the gene encoding the RUNX1 transcription factor, is observed in 25% of pediatric acute lymphoblastic leukemia (ALL) and is an initiating event in the disease. To elucidate the mechanism by which RUNX1 disruption initiates leukemogenesis, we investigated its normal role in murine B-cell development. This study revealed 2 critical functions of Runx1: (1) to promote survival and development of progenitors specified to the B-cell lineage, a function that can be substituted by ectopic Bcl2 expression, and (2) to enable the developmental transition through the pre-B stage triggered by the pre-B-cell antigen receptor (pre-BCR). Gene expression analysis and genomewide Runx1 occupancy studies support the hypothesis that Runx1 reinforces the transcription factor network governing early B-cell survival and development and specifically regulates genes encoding members of the Lyn kinase subfamily (key integrators of interleukin-7 and pre-BCR signaling) and the stage-specific transcription factors SpiB and Aiolos (critical downstream effectors of pre-BCR signaling). Interrogation of expression databases of 257 ALL samples demonstrated the specific down-regulation of the SPIB and IKZF3 genes (the latter encoding AIOLOS) in t(12;21) ALL, providing novel insight into the mechanism by which the translocation blocks B-cell development and promotes leukemia.

AB - The t(12;21) chromosomal translocation, targeting the gene encoding the RUNX1 transcription factor, is observed in 25% of pediatric acute lymphoblastic leukemia (ALL) and is an initiating event in the disease. To elucidate the mechanism by which RUNX1 disruption initiates leukemogenesis, we investigated its normal role in murine B-cell development. This study revealed 2 critical functions of Runx1: (1) to promote survival and development of progenitors specified to the B-cell lineage, a function that can be substituted by ectopic Bcl2 expression, and (2) to enable the developmental transition through the pre-B stage triggered by the pre-B-cell antigen receptor (pre-BCR). Gene expression analysis and genomewide Runx1 occupancy studies support the hypothesis that Runx1 reinforces the transcription factor network governing early B-cell survival and development and specifically regulates genes encoding members of the Lyn kinase subfamily (key integrators of interleukin-7 and pre-BCR signaling) and the stage-specific transcription factors SpiB and Aiolos (critical downstream effectors of pre-BCR signaling). Interrogation of expression databases of 257 ALL samples demonstrated the specific down-regulation of the SPIB and IKZF3 genes (the latter encoding AIOLOS) in t(12;21) ALL, providing novel insight into the mechanism by which the translocation blocks B-cell development and promotes leukemia.

KW - Animals

KW - Apoptosis

KW - B-Lymphocytes

KW - Binding Sites

KW - Cell Differentiation

KW - Cell Lineage

KW - Cell Proliferation

KW - Cell Survival

KW - Chromosomes, Human, Pair 12

KW - Chromosomes, Human, Pair 21

KW - Core Binding Factor Alpha 2 Subunit

KW - Enhancer Elements, Genetic

KW - Gene Deletion

KW - Gene Expression Regulation, Developmental

KW - Gene Expression Regulation, Leukemic

KW - Gene Targeting

KW - Genome

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

KW - Protein Binding

KW - Proto-Oncogene Proteins c-bcl-2

KW - Trans-Activators

KW - Translocation, Genetic

U2 - 10.1182/blood-2013-01-480244

DO - 10.1182/blood-2013-01-480244

M3 - SCORING: Journal article

C2 - 23704093

VL - 122

SP - 413

EP - 423

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 3

ER -