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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ferrata Storti Foundation
2017
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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. |
format | Online Article Text |
id | pubmed-5451336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
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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