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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.


ABSTRACT: 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.

SUBMITTER: Lin CC 

PROVIDER: S-EPMC5451336 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Lin Chien-Chin CC   Hsu Yueh-Chwen YC   Li Yi-Hung YH   Kuo Yuan-Yeh YY   Hou Hsin-An HA   Lan Keng-Hsueh KH   Chen Tsung-Chih TC   Tzeng Yi-Shiuan YS   Kuo Yi-Yi YY   Kao Chein-Jun CJ   Chuang Po-Han PH   Tseng Mei-Hsuan MH   Chiu Yu-Chiao YC   Chou Wen-Chien WC   Tien Hwei-Fang HF  

Haematologica 20170324 6


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 <i>HOX</i> family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of <i>HOPX</i> in the disease remain unknown. Thus we analyzed <i>HOPX</i> and global gene expression patterns in 347 newly diagnosed <i>de novo</i> AML patients in our institut  ...[more]

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