Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
| Autor: | Po-Han Chuang, Mei-Hsuan Tseng, Yi-Hung Li, Yi-Yi Kuo, Hsin-An Hou, Yi-Shiuan Tzeng, Yu-Chiao Chiu, Wen-Chien Chou, Tsung-Chih Chen, Yueh-Chwen Hsu, Chein-Jun Kao, Yuan-Yeh Kuo, Hwei-Fang Tien, Keng-Hsueh Lan, Chien-Chin Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Acute promyelocytic leukemia Acute Myeloid Leukemia Myeloid Biology Stem cell marker Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine CEBPA medicine Humans Homeodomain Proteins Gene Expression Profiling Tumor Suppressor Proteins Myeloid leukemia Hematology medicine.disease Hematopoietic Stem Cells Prognosis Gene expression profiling Leukemia Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure RUNX1 chemistry 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Female Transcriptome Nucleophosmin |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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