The Sal-Like 1 (Sall1) Protein Is Highly Expressed In Primary Bone Marrow Cells Derived From Patients With Acute Myeloid Leukemia
BLOOD(2009)
摘要
Abstract Abstract 1285 Poster Board I-307 Background SALL1 is a zinc finger transcription factor that maps to chromosome 16q12.1 in humans and chromosome 8D in mice. It is a transcription factor required for kidney development, and is mutated in patients with Townes-Brocks syndrome (TBS). We have created a mouse model of TBS that expresses a truncated SALL1 protein and observed that these mice displayed a syndrome consistent with myelodysplastic syndrome (MDS) that accelerates to acute myeloid leukemia (AML). The purpose of this study was to investigate whether SALL1 is expressed in AML patients. Materials and methods 50 bone marrow (BM) samples obtained from AML patients and 10 BM samples obtained from healthy donors were studied. BM samples were processed immediately upon receipt. Immunohistochemistry was performed on paraffin tissue sections of human BM using an anti-SALL1 antibody. RNA was extracted using the RNeasy Mini Kit (Qiagen). Quantitative RT-PCR was performed using the SYBR Green PCR Master Mix and SALL1 specific primers. SALL1 mRNA expression was normalized to RPL19, a ribosomal housekeeping gene. Western blotting was performed to confirm the presence of SALL1 at the protein level. Two AML cell lines (Kasumi-1 and -3) were also screened for SALL1 expression. Results 44/50 human BM AML samples displayed positive nuclear staining for SALL1. Samples taken from healthy controls showed no evidence of staining. 9/ 9 human BM AML samples showed increased SALL1 mRNA levels as compared to healthy controls with upregulation of SALL1 mRNA levels ranging from 3-fold to 1630-fold. High interpatient variability was observed. On average, SALL1 expression of AML patients was 225.1-fold greater than that of healthy controls (n=9, p=0.004). Western blotting confirmed upregulated SALL1 protein expression in AML BM with no expression seen in healthy controls. No SALL1 mRNA was detected in Kasumi-1 and -3 AML cell lines. i.) The majority of patient samples examined in this study demonstrated positive staining for SALL1. ii.) Consistent with its role as a transcription factor SALL1 histochemical staining was nuclear. iii.) SALL1 is highly expressed in human AML BM on the mRNA as well as on the protein level. iv.) No SALL1 mRNA was detected in AML cell lines. Conclusion Our data in mice and humans link the overexpression of SALL1 to AML. The absence of SALL1 in cell lines and its presence in the BM may indicate that SALL1 is confined to a relatively primitive cell. It is to be speculated that SALL1 has functional significance for the molecular pathogenesis of AML. Further studies to elaborate on its molecular functions and interactions are therefore clearly warranted and being conducted. Disclosures No relevant conflicts of interest to declare.
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关键词
sall1,acute myeloid leukemia,primary bone marrow cells,bone marrow,sal-like
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