YBX1 mediates translation of oncogenic transcripts to control cell competition in AML

Research output: Contribution to journal › Journal article › Research › peer-review

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YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. / Perner, Florian; Schnoeder, Tina M; Xiong, Yijun; Jayavelu, Ashok Kumar; Mashamba, Nomusa; Santamaria, Nuria Tubio; Huber, Nicolas; Todorova, Kristina; Hatton, Charles; Perner, Birgit; Eifert, Theresa; Murphy, Ciara; Hartmann, Maximilian; Hoell, Jessica I; Schröder, Nicolas; Brandt, Sabine; Hochhaus, Andreas; Mertens, Peter R; Mann, Matthias; Armstrong, Scott A; Mandinova, Anna; Heidel, Florian H.

In: Leukemia, Vol. 36, No. 2, 02.2022, p. 426-437.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Perner, F, Schnoeder, TM, Xiong, Y, Jayavelu, AK, Mashamba, N, Santamaria, NT, Huber, N, Todorova, K, Hatton, C, Perner, B, Eifert, T, Murphy, C, Hartmann, M, Hoell, JI, Schröder, N, Brandt, S, Hochhaus, A, Mertens, PR, Mann, M, Armstrong, SA, Mandinova, A & Heidel, FH 2022, 'YBX1 mediates translation of oncogenic transcripts to control cell competition in AML', Leukemia, vol. 36, no. 2, pp. 426-437. https://doi.org/10.1038/s41375-021-01393-0

APA

Perner, F., Schnoeder, T. M., Xiong, Y., Jayavelu, A. K., Mashamba, N., Santamaria, N. T., Huber, N., Todorova, K., Hatton, C., Perner, B., Eifert, T., Murphy, C., Hartmann, M., Hoell, J. I., Schröder, N., Brandt, S., Hochhaus, A., Mertens, P. R., Mann, M., ... Heidel, F. H. (2022). YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. Leukemia, 36(2), 426-437. https://doi.org/10.1038/s41375-021-01393-0

Vancouver

Perner F, Schnoeder TM, Xiong Y, Jayavelu AK, Mashamba N, Santamaria NT et al. YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. Leukemia. 2022 Feb;36(2):426-437. https://doi.org/10.1038/s41375-021-01393-0

Author

Perner, Florian ; Schnoeder, Tina M ; Xiong, Yijun ; Jayavelu, Ashok Kumar ; Mashamba, Nomusa ; Santamaria, Nuria Tubio ; Huber, Nicolas ; Todorova, Kristina ; Hatton, Charles ; Perner, Birgit ; Eifert, Theresa ; Murphy, Ciara ; Hartmann, Maximilian ; Hoell, Jessica I ; Schröder, Nicolas ; Brandt, Sabine ; Hochhaus, Andreas ; Mertens, Peter R ; Mann, Matthias ; Armstrong, Scott A ; Mandinova, Anna ; Heidel, Florian H. / YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. In: Leukemia. 2022 ; Vol. 36, No. 2. pp. 426-437.

Bibtex

@article{16c91b14dba54be696b699ab7e5bac40,
title = "YBX1 mediates translation of oncogenic transcripts to control cell competition in AML",
abstract = "Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.",
keywords = "Animals, Apoptosis, Biomarkers, Tumor/genetics, Cell Competition, Cell Proliferation, Humans, Janus Kinase 2/genetics, Leukemia, Myeloid, Acute/genetics, Mice, Mutation, Prognosis, Proto-Oncogene Proteins c-myc/genetics, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Y-Box-Binding Protein 1/genetics",
author = "Florian Perner and Schnoeder, {Tina M} and Yijun Xiong and Jayavelu, {Ashok Kumar} and Nomusa Mashamba and Santamaria, {Nuria Tubio} and Nicolas Huber and Kristina Todorova and Charles Hatton and Birgit Perner and Theresa Eifert and Ciara Murphy and Maximilian Hartmann and Hoell, {Jessica I} and Nicolas Schr{\"o}der and Sabine Brandt and Andreas Hochhaus and Mertens, {Peter R} and Matthias Mann and Armstrong, {Scott A} and Anna Mandinova and Heidel, {Florian H}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2022",
month = feb,
doi = "10.1038/s41375-021-01393-0",
language = "English",
volume = "36",
pages = "426--437",
journal = "Leukemia",
issn = "0887-6924",
publisher = "nature publishing group",
number = "2",

}

RIS

TY - JOUR

T1 - YBX1 mediates translation of oncogenic transcripts to control cell competition in AML

AU - Perner, Florian

AU - Schnoeder, Tina M

AU - Xiong, Yijun

AU - Jayavelu, Ashok Kumar

AU - Mashamba, Nomusa

AU - Santamaria, Nuria Tubio

AU - Huber, Nicolas

AU - Todorova, Kristina

AU - Hatton, Charles

AU - Perner, Birgit

AU - Eifert, Theresa

AU - Murphy, Ciara

AU - Hartmann, Maximilian

AU - Hoell, Jessica I

AU - Schröder, Nicolas

AU - Brandt, Sabine

AU - Hochhaus, Andreas

AU - Mertens, Peter R

AU - Mann, Matthias

AU - Armstrong, Scott A

AU - Mandinova, Anna

AU - Heidel, Florian H

N1 - © 2021. The Author(s).

PY - 2022/2

Y1 - 2022/2

N2 - Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

AB - Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

KW - Animals

KW - Apoptosis

KW - Biomarkers, Tumor/genetics

KW - Cell Competition

KW - Cell Proliferation

KW - Humans

KW - Janus Kinase 2/genetics

KW - Leukemia, Myeloid, Acute/genetics

KW - Mice

KW - Mutation

KW - Prognosis

KW - Proto-Oncogene Proteins c-myc/genetics

KW - Tumor Cells, Cultured

KW - Xenograft Model Antitumor Assays

KW - Y-Box-Binding Protein 1/genetics

U2 - 10.1038/s41375-021-01393-0

DO - 10.1038/s41375-021-01393-0

M3 - Journal article

C2 - 34465866

VL - 36

SP - 426

EP - 437

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 2

ER -

ID: 303116628