HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies

Miguel Gallardo; Hun Ju Lee; Xiaorui Zhang; Carlos Bueso-Ramos; Laura R. Pageon; Mark McArthur; Asha Multani; Aziz Nazha; Taghi Manshouri; Jan Parker-Thornburg; Inmaculada Rapado; Alfonso Quintas-Cardama; Steven M. Kornblau; Joaquin Martinez-Lopez; Sean M. Post

doi:10.1016/j.ccell.2015.09.001

HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies

Miguel Gallardo
, Hun Ju Lee
, Xiaorui Zhang
, Carlos Bueso-Ramos
, Laura R. Pageon
, Mark McArthur
, Asha Multani
, Aziz Nazha
, Taghi Manshouri
, Jan Parker-Thornburg
, Inmaculada Rapado
, Alfonso Quintas-Cardama
, Steven M. Kornblau
, Joaquin Martinez-Lopez
, Sean M. Post

Research output: Contribution to journal › Article › peer-review

125 Scopus citations

Abstract

hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk^+/-). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.

Original language	English
Article number	2143
Pages (from-to)	486-499
Number of pages	14
Journal	Cancer Cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2015.09.001
State	Published - 12 Oct 2015
Externally published	Yes

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10.1016/j.ccell.2015.09.001

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Gallardo, M., Lee, H. J., Zhang, X., Bueso-Ramos, C., Pageon, L. R., McArthur, M., Multani, A., Nazha, A., Manshouri, T., Parker-Thornburg, J., Rapado, I., Quintas-Cardama, A., Kornblau, S. M., Martinez-Lopez, J., & Post, S. M. (2015). HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. Cancer Cell, 28(4), 486-499. Article 2143. https://doi.org/10.1016/j.ccell.2015.09.001

@article{49785f8918fc4146b2c1b2158b5e5f9d,

title = "HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies",

abstract = "hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk+/-). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.",

author = "Miguel Gallardo and Lee, \{Hun Ju\} and Xiaorui Zhang and Carlos Bueso-Ramos and Pageon, \{Laura R.\} and Mark McArthur and Asha Multani and Aziz Nazha and Taghi Manshouri and Jan Parker-Thornburg and Inmaculada Rapado and Alfonso Quintas-Cardama and Kornblau, \{Steven M.\} and Joaquin Martinez-Lopez and Post, \{Sean M.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = oct,

day = "12",

doi = "10.1016/j.ccell.2015.09.001",

language = "English",

volume = "28",

pages = "486--499",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Gallardo, M, Lee, HJ, Zhang, X, Bueso-Ramos, C, Pageon, LR, McArthur, M, Multani, A, Nazha, A, Manshouri, T, Parker-Thornburg, J, Rapado, I, Quintas-Cardama, A, Kornblau, SM, Martinez-Lopez, J & Post, SM 2015, 'HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies', Cancer Cell, vol. 28, no. 4, 2143, pp. 486-499. https://doi.org/10.1016/j.ccell.2015.09.001

TY - JOUR

T1 - HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies

AU - Gallardo, Miguel

AU - Lee, Hun Ju

AU - Zhang, Xiaorui

AU - Bueso-Ramos, Carlos

AU - Pageon, Laura R.

AU - McArthur, Mark

AU - Multani, Asha

AU - Nazha, Aziz

AU - Manshouri, Taghi

AU - Parker-Thornburg, Jan

AU - Rapado, Inmaculada

AU - Quintas-Cardama, Alfonso

AU - Kornblau, Steven M.

AU - Martinez-Lopez, Joaquin

AU - Post, Sean M.

PY - 2015/10/12

Y1 - 2015/10/12

N2 - hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk+/-). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.

AB - hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk+/-). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.

UR - https://www.scopus.com/pages/publications/84944062849

U2 - 10.1016/j.ccell.2015.09.001

DO - 10.1016/j.ccell.2015.09.001

M3 - Article

C2 - 26412324

AN - SCOPUS:84944062849

SN - 1535-6108

VL - 28

SP - 486

EP - 499

JO - Cancer Cell

JF - Cancer Cell

IS - 4

M1 - 2143

ER -

HnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies

Abstract

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