The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Dimitrios Papaioannou; Andreas Petri; Oliver M Dovey; Sara Terreri; Eric Wang; Frances A Collins; Lauren A Woodward; Allison E Walker; Deedra Nicolet; Felice Pepe; Prasanthi Kumchala; Marius Bill; Christopher J Walker; Malith Karunasiri; Krzysztof Mrózek; Miranda L Gardner; Virginia Camilotto; Nina Zitzer; Jonathan L Cooper; Xiongwei Cai; Xiaoqing Rong-Mullins; Jessica Kohlschmidt; Kellie J Archer; Michael A Freitas; Yi Zheng; Robert J Lee; Iannis Aifantis; George Vassiliou; Guramrit Singh; Sakari Kauppinen; Clara D Bloomfield; Adrienne M Dorrance; Ramiro Garzon

doi:10.1038/s41467-019-13259-2

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Dimitrios Papaioannou, Andreas Petri, Oliver M Dovey, Sara Terreri, Eric Wang, Frances A Collins, Lauren A Woodward, Allison E Walker, Deedra Nicolet, Felice Pepe, Prasanthi Kumchala, Marius Bill, Christopher J Walker, Malith Karunasiri, Krzysztof Mrózek, Miranda L Gardner, Virginia Camilotto, Nina Zitzer, Jonathan L Cooper, Xiongwei CaiXiaoqing Rong-Mullins, Jessica Kohlschmidt, Kellie J Archer, Michael A Freitas, Yi Zheng, Robert J Lee, Iannis Aifantis, George Vassiliou, Guramrit Singh, Sakari Kauppinen, Clara D Bloomfield, Adrienne M Dorrance, Ramiro Garzon

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Abstract

Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

Original language	English
Article number	5351
Journal	Nature Communications
Volume	10
Issue number	1
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-13259-2
Publication status	Published - 25 Nov 2019

Bibliographical note

Publisher Correction:
"The original version of this Article contained an error in the author affiliations.
Affiliation number 9 incorrectly read “Department of Molecular Medicine, University of Pavia, Pavia, USA”
This has now been corrected in both the PDF and HTML versions of the Article."
(Nat Commun 11:204 (2020). https://doi.org/10.1038/s41467-019-13969-7).

Author Correction:
"The original version of this article omitted the following from the Acknowledgements: R.G. was supported by a Scholar in Clinical Research award from The Leukemia & Lymphoma Society."
This has now been corrected in both the PDF and HTML versions of the article.
(Nat Commun 11:3878 (2020). https://doi.org/10.1038/s41467-020-17746-9.

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Papaioannou, D., Petri, A., Dovey, O. M., Terreri, S., Wang, E., Collins, F. A., Woodward, L. A., Walker, A. E., Nicolet, D., Pepe, F., Kumchala, P., Bill, M., Walker, C. J., Karunasiri, M., Mrózek, K., Gardner, M. L., Camilotto, V., Zitzer, N., Cooper, J. L., ... Garzon, R. (2019). The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia. Nature Communications, 10(1), Article 5351. https://doi.org/10.1038/s41467-019-13259-2

@article{2a788162faa7475383f7a7a3265ccdd6,

title = "The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia",

abstract = "Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.",

author = "Dimitrios Papaioannou and Andreas Petri and Dovey, {Oliver M} and Sara Terreri and Eric Wang and Collins, {Frances A} and Woodward, {Lauren A} and Walker, {Allison E} and Deedra Nicolet and Felice Pepe and Prasanthi Kumchala and Marius Bill and Walker, {Christopher J} and Malith Karunasiri and Krzysztof Mr{\'o}zek and Gardner, {Miranda L} and Virginia Camilotto and Nina Zitzer and Cooper, {Jonathan L} and Xiongwei Cai and Xiaoqing Rong-Mullins and Jessica Kohlschmidt and Archer, {Kellie J} and Freitas, {Michael A} and Yi Zheng and Lee, {Robert J} and Iannis Aifantis and George Vassiliou and Guramrit Singh and Sakari Kauppinen and Bloomfield, {Clara D} and Dorrance, {Adrienne M} and Ramiro Garzon",

note = "Publisher Correction: {"}The original version of this Article contained an error in the author affiliations. Affiliation number 9 incorrectly read “Department of Molecular Medicine, University of Pavia, Pavia, USA” This has now been corrected in both the PDF and HTML versions of the Article.{"} (Nat Commun 11:204 (2020). https://doi.org/10.1038/s41467-019-13969-7). Author Correction: {"}The original version of this article omitted the following from the Acknowledgements: R.G. was supported by a Scholar in Clinical Research award from The Leukemia & Lymphoma Society.{"} This has now been corrected in both the PDF and HTML versions of the article. (Nat Commun 11:3878 (2020). https://doi.org/10.1038/s41467-020-17746-9. ",

year = "2019",

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doi = "10.1038/s41467-019-13259-2",

language = "English",

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Papaioannou, D, Petri, A, Dovey, OM, Terreri, S, Wang, E, Collins, FA, Woodward, LA, Walker, AE, Nicolet, D, Pepe, F, Kumchala, P, Bill, M, Walker, CJ, Karunasiri, M, Mrózek, K, Gardner, ML, Camilotto, V, Zitzer, N, Cooper, JL, Cai, X, Rong-Mullins, X, Kohlschmidt, J, Archer, KJ, Freitas, MA, Zheng, Y, Lee, RJ, Aifantis, I, Vassiliou, G, Singh, G, Kauppinen, S, Bloomfield, CD, Dorrance, AM & Garzon, R 2019, 'The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia', Nature Communications, vol. 10, no. 1, 5351. https://doi.org/10.1038/s41467-019-13259-2

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T1 - The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

AU - Papaioannou, Dimitrios

AU - Petri, Andreas

AU - Dovey, Oliver M

AU - Terreri, Sara

AU - Wang, Eric

AU - Collins, Frances A

AU - Woodward, Lauren A

AU - Walker, Allison E

AU - Nicolet, Deedra

AU - Pepe, Felice

AU - Kumchala, Prasanthi

AU - Bill, Marius

AU - Walker, Christopher J

AU - Karunasiri, Malith

AU - Mrózek, Krzysztof

AU - Gardner, Miranda L

AU - Camilotto, Virginia

AU - Zitzer, Nina

AU - Cooper, Jonathan L

AU - Cai, Xiongwei

AU - Rong-Mullins, Xiaoqing

AU - Kohlschmidt, Jessica

AU - Archer, Kellie J

AU - Freitas, Michael A

AU - Zheng, Yi

AU - Lee, Robert J

AU - Aifantis, Iannis

AU - Vassiliou, George

AU - Singh, Guramrit

AU - Kauppinen, Sakari

AU - Bloomfield, Clara D

AU - Dorrance, Adrienne M

AU - Garzon, Ramiro

N1 - Publisher Correction: "The original version of this Article contained an error in the author affiliations. Affiliation number 9 incorrectly read “Department of Molecular Medicine, University of Pavia, Pavia, USA” This has now been corrected in both the PDF and HTML versions of the Article." (Nat Commun 11:204 (2020). https://doi.org/10.1038/s41467-019-13969-7). Author Correction: "The original version of this article omitted the following from the Acknowledgements: R.G. was supported by a Scholar in Clinical Research award from The Leukemia & Lymphoma Society." This has now been corrected in both the PDF and HTML versions of the article. (Nat Commun 11:3878 (2020). https://doi.org/10.1038/s41467-020-17746-9.

PY - 2019/11/25

Y1 - 2019/11/25

N2 - Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

AB - Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

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U2 - 10.1038/s41467-019-13259-2

DO - 10.1038/s41467-019-13259-2

M3 - Journal article

C2 - 31767858

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5351

ER -

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

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