Other entities represented in this entry:
Cytogenetic location: 3q26 Genomic coordinates (GRCh38): 3:161,000,001-183,000,000
In leukemic cells of 4 patients with therapy-related myelodysplasia/acute myeloid leukemia and in 1 patient with chronic myelogenous leukemia in blast crisis, all of whom had a t(3;21)(q26;q22), Nucifora et al. (1994) consistently found fusion transcripts between AML1 (151385) and EAP (RPL22; 180474) or between AML1 and previously unidentified sequences that they named MDS1, for MDS-associated sequences. In addition, they identified a third chimeric transcript, AML1/EVI1 (165215), in 1 of the therapy-related acute myeloid leukemia patients.
MDS1 had been identified as a separate gene and also as a previously unreported exon (or exons) of EVI1. Fears et al. (1996) demonstrated 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-prime end of the previously reported EVI1 open reading frame. This additional region has about 40% homology at the amino acid level with the PR domain of the retinoblastoma-interacting zinc finger protein RIZ (601196). These results are important because EVI1 and MDS1 are involved in leukemia associated with chromosomal translocation breakpoints in the region between the genes (see CYTOGENETICS).
Mochizuki et al. (2000) referred to MDS1/EVI1 as an alternatively spliced transcript of EVI1.
Based on their involvement in a t(3;21)(q26;q22) translocation, Nucifora et al. (1994) mapped the MDS1, EVI1, and EAP genes to chromosome 3q26. Pulsed field gel electrophoresis established the order of the genes as EAP, the most telomeric, and EVI1, the most centromeric, with MDS1 situated between them. Fluorescence in situ hybridization confirmed that EVI1 is centromeric to MDS1. However, Uechi et al. (2001) reported that the RPL22 (EAP) gene maps to chromosome 1p36.3, not chromosome 3q26. They concluded that the RPL22 copy on chromosome 3q26 is a processed RPL22 pseudogene.
In leukemic cells of 4 patients with therapy-related myelodysplasia/acute myeloid leukemia and in 1 patient with chronic myelogenous leukemia in blast crisis, all of whom had a t(3;21)(q26;q22), Nucifora et al. (1994) consistently found fusion transcripts between AML1 (151385) and EAP (RPL22; 180474) or between AML1 and previously unidentified sequences that they named MDS1, for MDS-associated sequences. In addition, they identified a third chimeric transcript, AML1/EVI1 (165215), in 1 of the therapy-related acute myeloid leukemia patients.
Nucifora and Rowley (1995) reviewed the involvement of the AML1 gene in the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Three loci closely situated to each other on 3q26 are involved in fusions with AML1 in the 3;21 translocations: EVI1, EAP, and MDS1. They pointed out that the order of the genes on 3q26 is TEL--EAP--MDS1--EVI1 and provided a diagram (their Figure 5) of the 3q26 region containing these genes and of the various chimeric junctions they had isolated from t(3;21) patients. However, Uechi et al. (2001) reported that the RPL22 (EAP) gene maps to chromosome 1p36.3, not chromosome 3q26. They concluded that the chromosomal breakage on 3q26 reported by Nucifora et al. (1994) occurred in a processed RPL22 pseudogene.
Fears, S., Mathieu, C., Zeleznik-Le, N., Huang, S., Rowley, J. D., Nucifora, G. 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. Proc. Nat. Acad. Sci. 93: 1642-1647, 1996. [PubMed: 8643684] [Full Text: https://doi.org/10.1073/pnas.93.4.1642]
Mochizuki, N., Shimizu, S., Nagasawa, T., Tanaka, H., Taniwaki, M., Yokota, J., Morishita, K. A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood 96: 3209-3214, 2000. [PubMed: 11050005]
Nucifora, G., Begy, C. R., Kobayashi, H., Roulston, D., Claxton, D., Pedersen-Bjergaard, J., Parganas, E., Ihle, J. N., Rowley, J. D. Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations. Proc. Nat. Acad. Sci. 91: 4004-4008, 1994. [PubMed: 8171026] [Full Text: https://doi.org/10.1073/pnas.91.9.4004]
Nucifora, G., Rowley, J. D. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 86: 1-14, 1995. [PubMed: 7795214]
Uechi, T., Tanaka, T., Kenmochi, N. A complete map of the human ribosomal protein genes: assignment of 80 genes to the cytogenetic map and implications for human disorders. Genomics 72: 223-230, 2001. [PubMed: 11401437] [Full Text: https://doi.org/10.1006/geno.2000.6470]