Abstract

BackgroundMyelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course. Predicting disease progression is difficult due to lack of specific molecular marker(s). SALL4 plays important roles in normal hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to acute myeloid leukemia (AML) transformation. However, the role of SALL4 in human MDS has not been extensively investigated. In this study, we evaluate the diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in a cohort of MDS patients.MethodsFifty-five newly diagnosed MDS, twenty MDS-AML, and sixteen post-treatment MDS patients were selected for our study along with ten healthy donors.ResultsWe demonstrated that SALL4 was over-expressed in MDS patients and proportionally increased in MDS patients with high grade/IPSS scores. This expression pattern was similar to that of Bmi-1, an important marker in predicting MDS/AML progression. In addition, the level of SALL4 was positively correlated with increased blast counts, high-risk keryotypes and increased significantly in MDS-AML transformation. Furthermore, higher level of SALL4 expression was associated with worse survival rates and SALL4 level decreased following effective therapy.ConclusionsTo the best of our knowledge, this is the largest series and the first to report the expression pattern of SALL4 in detail in various subtypes of MDS in comparison to that of Bmi-1. We conclude that SALL4 is a potential molecular marker in predicting the prognosis of MDS.

Highlights

  • Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course

  • Since MDS is a pre-leukemic stage of acute myeloid leukemia (AML) [32] and the expression pattern of SALL4 in human MDS hasn’t been intensively investigated, in this study we evaluate the expression of SALL4 in various MDS patients compared to that of Bmi-1 to explore the potential clinical prognostic value of SALL4 in MDS

  • We noticed that SALL4 expression measured by microarray was higher (p

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Summary

Introduction

Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course. SALL4 plays important roles in normal hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to acute myeloid leukemia (AML) transformation. We evaluate the diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in a cohort of MDS patients. Because of its heterogeneity and lack of molecular markers that effectively monitor disease progression, clinical management of MDS patients is challenging. SALL4 is an important embryonic stem cell (ESC) factor that is involved in normal hematopoiesis, leukemogenesis [12,13,14,15,16,17,18,19,20], hepatocellular carcinoma [21,22,23] and infantile hemangiomas [24]. We have demonstrated recently that the expression level of SALL4 was related to AML treatment status [16]. SALL4 expression levels declined during the treatment process in the drug responsive group and increased in the drug resistant group

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