PortalPublikationenGrb10 is involved in BCR-ABL-positive leukemia in mice

Grb10 is involved in BCR-ABL-positive leukemia in mice

Standard

Grb10 is involved in BCR-ABL-positive leukemia in mice. / Illert, A L; Albers, C; Kreutmair, S; Leischner, H; Peschel, C; Miething, C; Duyster, J.

in: LEUKEMIA, Jahrgang 29, Nr. 4, 04.2015, S. 858-68.

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

Harvard

Illert, AL, Albers, C, Kreutmair, S, Leischner, H, Peschel, C, Miething, C & Duyster, J 2015, 'Grb10 is involved in BCR-ABL-positive leukemia in mice', LEUKEMIA, Jg. 29, Nr. 4, S. 858-68. https://doi.org/10.1038/leu.2014.283

APA

Illert, A. L., Albers, C., Kreutmair, S., Leischner, H., Peschel, C., Miething, C., & Duyster, J. (2015). Grb10 is involved in BCR-ABL-positive leukemia in mice. LEUKEMIA, 29(4), 858-68. https://doi.org/10.1038/leu.2014.283

Vancouver

Illert AL, Albers C, Kreutmair S, Leischner H, Peschel C, Miething C et al. Grb10 is involved in BCR-ABL-positive leukemia in mice. LEUKEMIA. 2015 Apr;29(4):858-68. https://doi.org/10.1038/leu.2014.283

Bibtex

@article{c82e684e29e44a299f7e343f7f6db775,
title = "Grb10 is involved in BCR-ABL-positive leukemia in mice",
abstract = "The SH2-containing adaptor protein Grb10 was first identified in a yeast screen as a new binding partner for BCR-ABL and associates with BCR-ABL in a tyrosine-dependent manner. However, its function in BCR-ABL-mediated leukemogenesis in vivo is still unknown. Here we describe an important role of Grb10 in BCR-ABL-induced leukemia by using a versatile system for efficient oncogene expression and simultaneous Grb10 knockdown from a single vector. Primary bone marrow (BM) cells coexpressing Grb10-miR/BCR-ABL showed a significant decrease in colony formation and cell cycle progression. Transplantation of Grb10miR/BCR-ABL- or control-miR/BCR-ABL- transduced BM leads to a CML/B-ALL-like phenotype with significantly delayed disease onset and progression resulting in prolonged overall survival in Grb10-miR-transplanted mice. Methylcellulose experiments exhibit additive effects of imatinib treatment and Grb10 knockdown. Cell cycle analysis suggests an anti-proliferative effect of Grb10 knockdown in BCR-ABL(+) primary BM cells. However, Grb10 abrogation was not capable of completely abolishing the BCR-ABL-induced disease. Our findings were confirmed in the human BCR-ABL(+) cell line K562, where we demonstrate reduced viability, cell cycle progression and induction of apoptosis by stable Grb10 microRNA expression. Taken together, our results suggest that Grb10 knockdown in vivo leads to impaired proliferation, longer survival and reduced colony formation, suggesting an important role of Grb10 in BCR-ABL-mediated leukemogenesis. ",
keywords = "Animals, Antineoplastic Agents, Apoptosis, Benzamides, Bone Marrow Cells, Cell Cycle, Cell Proliferation, Disease Models, Animal, Female, Fusion Proteins, bcr-abl, GRB10 Adaptor Protein, Gene Expression Regulation, Leukemic, Humans, Imatinib Mesylate, K562 Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Mice, Mice, Inbred BALB C, MicroRNAs, Piperazines, Primary Cell Culture, Pyrimidines, RNA, Small Interfering, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't",
author = "Illert, {A L} and C Albers and S Kreutmair and H Leischner and C Peschel and C Miething and J Duyster",
year = "2015",
month = apr,
doi = "10.1038/leu.2014.283",
language = "English",
volume = "29",
pages = "858--68",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "4",

}

RIS

TY - JOUR

T1 - Grb10 is involved in BCR-ABL-positive leukemia in mice

AU - Illert, A L

AU - Albers, C

AU - Kreutmair, S

AU - Leischner, H

AU - Peschel, C

AU - Miething, C

AU - Duyster, J

PY - 2015/4

Y1 - 2015/4

N2 - The SH2-containing adaptor protein Grb10 was first identified in a yeast screen as a new binding partner for BCR-ABL and associates with BCR-ABL in a tyrosine-dependent manner. However, its function in BCR-ABL-mediated leukemogenesis in vivo is still unknown. Here we describe an important role of Grb10 in BCR-ABL-induced leukemia by using a versatile system for efficient oncogene expression and simultaneous Grb10 knockdown from a single vector. Primary bone marrow (BM) cells coexpressing Grb10-miR/BCR-ABL showed a significant decrease in colony formation and cell cycle progression. Transplantation of Grb10miR/BCR-ABL- or control-miR/BCR-ABL- transduced BM leads to a CML/B-ALL-like phenotype with significantly delayed disease onset and progression resulting in prolonged overall survival in Grb10-miR-transplanted mice. Methylcellulose experiments exhibit additive effects of imatinib treatment and Grb10 knockdown. Cell cycle analysis suggests an anti-proliferative effect of Grb10 knockdown in BCR-ABL(+) primary BM cells. However, Grb10 abrogation was not capable of completely abolishing the BCR-ABL-induced disease. Our findings were confirmed in the human BCR-ABL(+) cell line K562, where we demonstrate reduced viability, cell cycle progression and induction of apoptosis by stable Grb10 microRNA expression. Taken together, our results suggest that Grb10 knockdown in vivo leads to impaired proliferation, longer survival and reduced colony formation, suggesting an important role of Grb10 in BCR-ABL-mediated leukemogenesis.

AB - The SH2-containing adaptor protein Grb10 was first identified in a yeast screen as a new binding partner for BCR-ABL and associates with BCR-ABL in a tyrosine-dependent manner. However, its function in BCR-ABL-mediated leukemogenesis in vivo is still unknown. Here we describe an important role of Grb10 in BCR-ABL-induced leukemia by using a versatile system for efficient oncogene expression and simultaneous Grb10 knockdown from a single vector. Primary bone marrow (BM) cells coexpressing Grb10-miR/BCR-ABL showed a significant decrease in colony formation and cell cycle progression. Transplantation of Grb10miR/BCR-ABL- or control-miR/BCR-ABL- transduced BM leads to a CML/B-ALL-like phenotype with significantly delayed disease onset and progression resulting in prolonged overall survival in Grb10-miR-transplanted mice. Methylcellulose experiments exhibit additive effects of imatinib treatment and Grb10 knockdown. Cell cycle analysis suggests an anti-proliferative effect of Grb10 knockdown in BCR-ABL(+) primary BM cells. However, Grb10 abrogation was not capable of completely abolishing the BCR-ABL-induced disease. Our findings were confirmed in the human BCR-ABL(+) cell line K562, where we demonstrate reduced viability, cell cycle progression and induction of apoptosis by stable Grb10 microRNA expression. Taken together, our results suggest that Grb10 knockdown in vivo leads to impaired proliferation, longer survival and reduced colony formation, suggesting an important role of Grb10 in BCR-ABL-mediated leukemogenesis.

KW - Animals

KW - Antineoplastic Agents

KW - Apoptosis

KW - Benzamides

KW - Bone Marrow Cells

KW - Cell Cycle

KW - Cell Proliferation

KW - Disease Models, Animal

KW - Female

KW - Fusion Proteins, bcr-abl

KW - GRB10 Adaptor Protein

KW - Gene Expression Regulation, Leukemic

KW - Humans

KW - Imatinib Mesylate

KW - K562 Cells

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive

KW - Mice

KW - Mice, Inbred BALB C

KW - MicroRNAs

KW - Piperazines

KW - Primary Cell Culture

KW - Pyrimidines

KW - RNA, Small Interfering

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/leu.2014.283

DO - 10.1038/leu.2014.283

M3 - SCORING: Journal article

C2 - 25249015

VL - 29

SP - 858

EP - 868

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 4

ER -