Study On The Role Of Evi-1 And MDS1-Evi-1 Genes In Pathogenesis Of Myelodysplastic Syndromes

The ecotropic virus integration site-1(Evi-1)gene,located at chromosome band 3q26, was originally described as a common retrovirus integration site.It was shown to be causally related to the development of retrovirus-induced murine acute myeloid leukemia (AML).The MDS1 gene was originally identified in myelodysplastic syndromes (MDS), and named the MDS-associated gene(MDS1).MDS1,located at 170~400kb upstream of Evi-1 was transcripted either as a individual gene or as a fusion gene (MDS1-Evi-1) with Evi-1 by different intergenic splicing.We detected the expression of Evi-1 and MDS1-Evi-1 in patients with MDS and post-MDS AML,and investigated its role in pathogenesis of the malignant diseases and its relation to ineffective hematopoiesis and dyshemopoiesis in MDS.In addition,we also observed the inhibition of proliferation of HEL cells by the Evi-1 antisense nucleotide in vitro culture. Results:1. Evi-1 expression was undetectable (Evi-1-negative) in the bone marrow cells from 8 healthy volunteers.Of them,3 showed MDS1-Evi-1 expression,but the ratio of MDS1-Evi-1/GAPDH (M-E/G) was low(<0.1).Neither Evi-1 nor MDS1-Evi-1 expression was detected in 5 anemia controls.2. Evi-1 transcripts were detected (Evi-1-positive) in 16 of 33 MDS patients (1/8RA, 9/14 RAEB,6/10 RAEB-T,0/1CMML).The positive rate of Evi-1 expression in RAEB(T) was higher than that in RA (p<0.05).Twenty of the 33 MDS patients (5/8RA,10/14 RAEB,5/10 RAEB-T, 0/1CMML) expressed MDS1-Evi-1 and M-E/G were all above 0.1.3. Evi-1 expression was positive in 6 Of 9 post-MDS AML while only in 5 of 34 de novo AML patients (p<0.01).MDS1-Evi-1 expression was found in 6 of 9 post-MDS AML and 8 of 34 de novo AML patients (p<0.05).4. None of the MDS patients showed abnormality involving chromosome 3, but Evi-1 expression was detected in 7/8 patients with -7.5. There was no difference in the parameters associated with apoptosis of bone marrow cells between Evi-1/MDS1-Evi-1 positive and negative MDS patients,but the yields of CFU-GM, CFU-E,BFU-E were lower in Evi-1/MDS1-Evi-1 positive patients.6. Dyserythropoiesis and dysgranulopoiesis in Evi-1 or MDS1-Evi-1 potisive MDS patients were similar to those in Evi-1 or MDS1-Evi-1 negative patients,but Evi-1 expression levels...