Hypoxia-inducible factor-1α expression indicates poor prognosis in myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS), which are clonal bone marrow malignancies characterized by ineffective hematopoiesis, incorporate a variety of disorders and have variable prognosis. Although the International Prognostic Scoring System (IPSS) provides a clinical model for risk stratification of patients with primary MDS, notable variability in prognosis is still observed within the same IPSS category. Hypoxia-inducible factor-1α (HIF-1α) is associated with an adverse prognosis in patients with solid tumors and some hematological malignancies. However, the relationship between HIF-1α and clinical outcomes of patients with MDS is unknown. We examined HIF-1α by immunohistochemistry in bone marrow specimens from 81 patients with MDS. Results showed that the expression rate of HIF-1α was 49.4% (40/81). Multivariate analysis including age, bone marrow blast percentage, cytogenetics, hemoglobin, white blood cell count and IPSS score demonstrated that HIF-1α (p = 0.049, HR = 2.704) was an independent prognostic indicator for MDS. Furthermore, the expression of HIF-1α was correlated with poor overall survival (p < 0.001) and disease progression (p = 0.004). In addition, correlation analysis revealed that the expression of HIF-1α was associated with bone marrow blast percentage (p < 0.001, r = 0.510), hemoglobin count (p < 0.001, r = 0.649) and cytogenetics (p = 0.009, r = 0.287). We also found that decitabine achieved a better therapeutic effect compared to traditional chemotherapy in HIF-1α positive patients. In conclusion, these results suggest that HIF-1α is a vital biomarker for predicting the progression and prognosis of MDS.

Keywords::

• Myelodysplastic syndromes
• hypoxia
• hypoxia-inducible factor-1α
• immunohistochemistry

Acknowledgements

This research was supported by grants from the National Natural Science Foundation of China (No. 30870914) and Medical Scientific Research Foundation of Zhejiang Province (No. 2009B046), and also assistance from the Case Management Center and Pathology Department of the First Affiliated Hospital, College of Medicine, Zhejiang University.

Potential conflict of interest

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