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Leukemia and Lymphoma 2012-Dec

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

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Hongyan Tong
Chao Hu
Zhengping Zhuang
Lijun Wang
Jie Jin

Nyckelord

Abstrakt

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.

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