Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in 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 family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of in the disease remain unknown. Thus we analyzed and global gene expression patterns in 347 newly diagnosed AML patients in our institute. We found that higher expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in , and , but negatively associated with acute promyelocytic leukemia, favorable karyotypes, double mutations and mutation. Patients with higher expression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higher 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 expression was associated with both hematopoietic and leukemia stem cell signatures. While and 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 to be a unique homeobox gene. Therefore, is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients.