Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

T. H. Liu; Y. J. Tang; Y. Huang; L. Wang; X. L. Guo; J. Q. Mi; L. G. Liu; H. Zhu; Y. Zhang; L. Chen; X. Liu; L. H. Zhang; Q. J. Ye; B. S. Li; J. Y. Tang; A. Ford; T. Enver; F. Liu; G. Q. Chen; D. L. Hong

doi:10.1038/leu.2016.313

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

T. H. Liu, Y. J. Tang, Y. Huang, L. Wang, X. L. Guo, J. Q. Mi, L. G. Liu, H. Zhu, Y. Zhang, L. Chen, X. Liu, L. H. Zhang, Q. J. Ye, B. S. Li, J. Y. Tang, A. Ford, T. Enver, F. Liu, G. Q. Chen, D. L. Hong

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

6 Scopus citations

Abstract

The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

Original language	English (US)
Pages (from-to)	1079-1086
Number of pages	8
Journal	Leukemia
Volume	31
Issue number	5
DOIs	https://doi.org/10.1038/leu.2016.313
State	Published - May 1 2017
Externally published	Yes

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

Access to Document

10.1038/leu.2016.313

Cite this

Liu, T. H., Tang, Y. J., Huang, Y., Wang, L., Guo, X. L., Mi, J. Q., Liu, L. G., Zhu, H., Zhang, Y., Chen, L., Liu, X., Zhang, L. H., Ye, Q. J., Li, B. S., Tang, J. Y., Ford, A., Enver, T., Liu, F., Chen, G. Q., & Hong, D. L. (2017). Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin. Leukemia, 31(5), 1079-1086. https://doi.org/10.1038/leu.2016.313

@article{e62fc2d3a51e4af683a510660d1db451,

title = "Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin",

abstract = "The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.",

author = "Liu, {T. H.} and Tang, {Y. J.} and Y. Huang and L. Wang and Guo, {X. L.} and Mi, {J. Q.} and Liu, {L. G.} and H. Zhu and Y. Zhang and L. Chen and X. Liu and Zhang, {L. H.} and Ye, {Q. J.} and Li, {B. S.} and Tang, {J. Y.} and A. Ford and T. Enver and F. Liu and Chen, {G. Q.} and Hong, {D. L.}",

note = "Funding Information: We thank M Greaves for critical comments on the paper. We thank B Zhang for the provision of fev:GFP zebrafish. B Zhao and C Duan are also acknowledged for their technical assistance in flow-sorting and mouse injection, respectively. This work was supported by grants from the National Basic Research Program of China (Grant No. 2012CB967001 to D-LH and 2010CB945300 and 2011CB943900 to FL) and the National Natural Science Foundation of China (Grant Nos. 81120108006, 90919055 and 91442106 to D-LH and 31425016 to FL). Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",

year = "2017",

month = may,

day = "1",

doi = "10.1038/leu.2016.313",

language = "English (US)",

volume = "31",

pages = "1079--1086",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

AU - Liu, T. H.

AU - Tang, Y. J.

AU - Huang, Y.

AU - Wang, L.

AU - Guo, X. L.

AU - Mi, J. Q.

AU - Liu, L. G.

AU - Zhu, H.

AU - Zhang, Y.

AU - Chen, L.

AU - Liu, X.

AU - Zhang, L. H.

AU - Ye, Q. J.

AU - Li, B. S.

AU - Tang, J. Y.

AU - Ford, A.

AU - Enver, T.

AU - Liu, F.

AU - Chen, G. Q.

AU - Hong, D. L.

N1 - Funding Information: We thank M Greaves for critical comments on the paper. We thank B Zhang for the provision of fev:GFP zebrafish. B Zhao and C Duan are also acknowledged for their technical assistance in flow-sorting and mouse injection, respectively. This work was supported by grants from the National Basic Research Program of China (Grant No. 2012CB967001 to D-LH and 2010CB945300 and 2011CB943900 to FL) and the National Natural Science Foundation of China (Grant Nos. 81120108006, 90919055 and 91442106 to D-LH and 31425016 to FL). Publisher Copyright: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

AB - The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

UR - http://www.scopus.com/inward/record.url?scp=85001759314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85001759314&partnerID=8YFLogxK

U2 - 10.1038/leu.2016.313

DO - 10.1038/leu.2016.313

M3 - Article

C2 - 27807368

AN - SCOPUS:85001759314

SN - 0887-6924

VL - 31

SP - 1079

EP - 1086

JO - Leukemia

JF - Leukemia

IS - 5

ER -

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this