Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia
Chien-Chin Lin,
Yueh-Chwen Hsu,
Yi-Hung Li,
Yuan-Yeh Kuo,
Hsin-An Hou,
Keng-Hsueh Lan,
Tsung-Chih Chen,
Yi-Shiuan Tzeng,
Yi-Yi Kuo,
Chein-Jun Kao,
Po-Han Chuang,
Mei-Hsuan Tseng,
Yu-Chiao Chiu,
Wen-Chien Chou,
Hwei-Fang Tien
Affiliations
Chien-Chin Lin
Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan;Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
Yueh-Chwen Hsu
Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
Yi-Hung Li
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Yuan-Yeh Kuo
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
Hsin-An Hou
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Keng-Hsueh Lan
Division of Radiation Oncology and Department of Oncology, National Taiwan University, Taipei, Taiwan
Tsung-Chih Chen
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Yi-Shiuan Tzeng
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
Yi-Yi Kuo
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Chein-Jun Kao
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Po-Han Chuang
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Mei-Hsuan Tseng
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Yu-Chiao Chiu
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
Wen-Chien Chou
Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan;Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Hwei-Fang Tien
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
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.
