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Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia

Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as the HOX family have been well characterized in acute myeloid leukemia (AML), the clinical and biologic...

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Autores principales: Lin, Chien-Chin, Hsu, Yueh-Chwen, Li, Yi-Hung, Kuo, Yuan-Yeh, Hou, Hsin-An, Lan, Keng-Hsueh, Chen, Tsung-Chih, Tzeng, Yi-Shiuan, Kuo, Yi-Yi, Kao, Chein-Jun, Chuang, Po-Han, Tseng, Mei-Hsuan, Chiu, Yu-Chiao, Chou, Wen-Chien, Tien, Hwei-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451336/
https://www.ncbi.nlm.nih.gov/pubmed/28341738
http://dx.doi.org/10.3324/haematol.2016.161257
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author Lin, Chien-Chin
Hsu, Yueh-Chwen
Li, Yi-Hung
Kuo, Yuan-Yeh
Hou, Hsin-An
Lan, Keng-Hsueh
Chen, Tsung-Chih
Tzeng, Yi-Shiuan
Kuo, Yi-Yi
Kao, Chein-Jun
Chuang, Po-Han
Tseng, Mei-Hsuan
Chiu, Yu-Chiao
Chou, Wen-Chien
Tien, Hwei-Fang
author_facet Lin, Chien-Chin
Hsu, Yueh-Chwen
Li, Yi-Hung
Kuo, Yuan-Yeh
Hou, Hsin-An
Lan, Keng-Hsueh
Chen, Tsung-Chih
Tzeng, Yi-Shiuan
Kuo, Yi-Yi
Kao, Chein-Jun
Chuang, Po-Han
Tseng, Mei-Hsuan
Chiu, Yu-Chiao
Chou, Wen-Chien
Tien, Hwei-Fang
author_sort Lin, Chien-Chin
collection PubMed
description Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as the HOX family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo AML patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation. Patients with higher HOPX expression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higher HOPX expression was an independent unfavorable prognostic factor irrespective of other known prognostic parameters and gene signatures derived from multiple cohorts. Gene set enrichment analysis showed higher HOPX expression was associated with both hematopoietic and leukemia stem cell signatures. While HOPX and HOX family genes showed concordant expression patterns in normal hematopoietic stem/progenitor cells, their expression patterns and associated clinical and biological features were distinctive in AML settings, demonstrating HOPX to be a unique homeobox gene. Therefore, HOPX is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients.
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spelling pubmed-54513362017-06-02 Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia Lin, Chien-Chin Hsu, Yueh-Chwen Li, Yi-Hung Kuo, Yuan-Yeh Hou, Hsin-An Lan, Keng-Hsueh Chen, Tsung-Chih Tzeng, Yi-Shiuan Kuo, Yi-Yi Kao, Chein-Jun Chuang, Po-Han Tseng, Mei-Hsuan Chiu, Yu-Chiao Chou, Wen-Chien Tien, Hwei-Fang Haematologica Article Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as the HOX family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo AML patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation. Patients with higher HOPX expression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higher HOPX expression was an independent unfavorable prognostic factor irrespective of other known prognostic parameters and gene signatures derived from multiple cohorts. Gene set enrichment analysis showed higher HOPX expression was associated with both hematopoietic and leukemia stem cell signatures. While HOPX and HOX family genes showed concordant expression patterns in normal hematopoietic stem/progenitor cells, their expression patterns and associated clinical and biological features were distinctive in AML settings, demonstrating HOPX to be a unique homeobox gene. Therefore, HOPX is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients. Ferrata Storti Foundation 2017-06 /pmc/articles/PMC5451336/ /pubmed/28341738 http://dx.doi.org/10.3324/haematol.2016.161257 Text en Copyright© Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Lin, Chien-Chin
Hsu, Yueh-Chwen
Li, Yi-Hung
Kuo, Yuan-Yeh
Hou, Hsin-An
Lan, Keng-Hsueh
Chen, Tsung-Chih
Tzeng, Yi-Shiuan
Kuo, Yi-Yi
Kao, Chein-Jun
Chuang, Po-Han
Tseng, Mei-Hsuan
Chiu, Yu-Chiao
Chou, Wen-Chien
Tien, Hwei-Fang
Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title_full Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title_fullStr Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title_full_unstemmed Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title_short Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
title_sort higher hopx expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451336/
https://www.ncbi.nlm.nih.gov/pubmed/28341738
http://dx.doi.org/10.3324/haematol.2016.161257
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