Disease relevance of MDS1

• Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family [1].
• Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders [2].
• Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: a model for human AML [3].
• Both fusion partners of AME, AML1 and MDS1/EVI1, encode transcription factors and are also targets of a variety of genetic abnormalities in human hematologic malignancies [4].
• Two of the clones (MDS1 and MDS3) had an insert of 1498 nucleotides showing typical signatures of spirochete 16S rRNA sequences [5].

High impact information on MDS1

• Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 [6].
• Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals [6].
• This murine model for AME-induced AML will help dissect the molecular mechanism of AML and the molecular biology of the AML1, MDS1, and EVI1 genes [3].
• These results are important in view of the fact that EVI1 and MDS1 are involved in leukemia associated with chromosomal translocation breakpoints in the region between these genes [1].
• In this report, we present evidence indicating that MDS1 exists in normal tissues both as a unique transcript and as a normal fusion transcript with EVI1, with an additional 188 codons at the 5' end of the previously reported EVI1 open reading frame [1].

Biological context of MDS1

• EVI-1 and its variant form, MDS1/EVI1, have been reported to act in an antagonistic manner and be differentially regulated in samples from patients with acute myeloid leukaemia and rearrangements of the long arm of chromosome 3 [7].
• The resulting chimeric transcript consists of the first two exons of ETV6 fused to MDS1 sequences, which in turn is fused to the second exon of the EVI1 gene [2].
• Furthermore, a comparison can be made with the formation of an AML1/MDS1/EVI1 fusion gene in translocations (3;21)(q26;q22) [2].
• In this study, genes were searched near the breakpoints at 1p36.3, and a novel gene was isolated that encoded a zinc finger protein with a PR domain, which is highly homologous to the MDS1/EVI1 gene [8].
• The novel gene, designated as MEL1 (MDS1/EVI1-like gene 1), with 1257 amino acid residues is 64% similar in nucleotide and 63% similar in amino acid sequences to MDS1/EVI1 with the same domain structure [8].

Anatomical context of MDS1

• The chromosomal breakpoint at 3q26 of HNT-34 cell line was located to approximately 200 kb 5' of FIM3 locus and more upstream of the MDS1. which is the same region as that of somatic cell hybrid line H10C [9].
• Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells [10].
• The aim of this study was to assess whether bone marrow CD34+ cell numbers could be used in differentiating between AA and hMDS [11].

Associations of MDS1 with chemical compounds

• Targeted Degradation of the AML1/MDS1/EVI1 Oncoprotein by Arsenic Trioxide [4].

Other interactions of MDS1

• AME is obtained by in-frame fusion of the AML1 and MDS1/EVI1 genes [12].
• In some of these samples, MDS1/EVI1 was also transcribed at elevated levels compared to those of healthy controls [13].
• The two genes are EAP, which codes for the abundant ribosomal protein L22, and MDS1, which encodes a small polypeptide of unknown function [14].
• We identified rare structural rearrangements in childhood acute myeloblastic leukemia, involving 3q21 and 3q26 loci around RPN1 and MDS1/EVI1 respectively [15].
• For all protocols, the immunostained cells were visualized by the same alkaline-phosphatase (AP) detection system (APAAP) followed by detection of the cells by manual screening and by two different automated screening systems (ACIS from Chromavision and MDS1 from Applied Imaging) [16].

Analytical, diagnostic and therapeutic context of MDS1

• In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34+ cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals [10].
• To discriminate between EVI1 and MDS1-EVI1 transcripts, distinct real-time quantitative polymerase chain reaction (PCR) assays were developed [17].

References