Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis inde novoacute 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 theHOXfamily have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications ofHOPXin the disease remain unknown. Thus we analyzedHOPXand global gene expression patterns in 347 newly diagnosedde novoAML patients in our institute. We found that higherHOPXexpression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations inRUNX1, IDH2, ASXL1, andDNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes,CEBPAdouble mutations andNPM1mutation. Patients with higherHOPXexpression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higherHOPXexpression was an independent unfavorable prognostic factor irrespective of other known prognostic parameters and gene signatures derived from multiple cohorts. Gene set enrichment analysis showed higherHOPXexpression was associated with both hematopoietic and leukemia stem cell signatures. WhileHOPXandHOXfamily 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, demonstratingHOPXto be a unique homeobox gene. Therefore,HOPXis a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients.
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.
Chien-Chin
CC
Lin
Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.
Yueh-Chwen
YC
Hsu
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Hung
YH
Li
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yuan-Yeh
YY
Kuo
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Hsin-An
HA
Hou
Division of Radiation Oncology and Department of Oncology, National Taiwan University, Taipei, Taiwan.
Keng-Hsueh
KH
Lan
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Tsung-Chih
TC
Chen
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Shiuan
YS
Tzeng
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Yi
YY
Kuo
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Chein-Jun
CJ
Kao
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Po-Han
PH
Chuang
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Mei-Hsuan
MH
Tseng
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan wchou@ntu.edu.tw f99945006@ntu.edu.tw hftien@ntu.edu.tw.
Yu-Chiao
YC
Chiu
Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan wchou@ntu.edu.tw f99945006@ntu.edu.tw hftien@ntu.edu.tw.|Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Wen-Chien
WC
Chou
Division of Hematology and Department of Internal Medicine, National Taiwan University, Taipei, Taiwan wchou@ntu.edu.tw f99945006@ntu.edu.tw hftien@ntu.edu.tw.
Hwei-Fang
HF
Tien
D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000473:pathology*; D014411:Neoplastic Stem Cells; D000090243:Nucleophosmin; D011379:Prognosis; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*
C476884:HOPX protein, human; D018398:Homeodomain Proteins; C000716967:NPM1 protein, human; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin