Translocations with a breakpoint at 11q23 are found in many leukemias (see MIM:159555; Winters and Bernt, 2017, pubmed:28232907; and the COSMIC links in the 'External links' section, below). These translocations involve the N-terminal portion of the mixed lineage leukemia gene (MLL, now designated KMT2A) fused to >80 different partner genes, including AF9 (now MLLT3), AF4 (now AFF1), and AF10 (now MLLT10). KMT2A (MLL, MLL1) encodes an H3K4 histone methyltransferase that plays an essential role in epigenetic regulation of gene expression during early development and hematopoiesis. MLLT3, AFF1, and MLLT10 encode proteins involved in aspects of transcriptional regulation and/or the process of transcription.
UAS constructs of three human MLL-AF fusion genes have been introduced into Drosophila: MLL-AF9 (Hsap\KMT2A::Hsap\MLLT3), MLL-AF4 (Hsap\KMT2A::Hsap\AFF1), and MLL-AF10 (Hsap\KMT2A::Hsap\MLLT10). For MLL-AF9 and MLL-AF4, the impact upon cell cycle progression and chromosome morphology have been investigated. In the case of MLL-AF10, protein domains and action of the orthologous Drosophila gene, Dmel\Alh, have compared to that of the Hsap\KMT2A::Hsap\MLLT10 fusion and to a Drosophila-human fusion (Alh::Hsap\KMT2A).
[updated Nov. 2019 by FlyBase; FBrf0222196]
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults; it is uncommon under age 40. (Most childhood leukemias are acute lymphocytic leukemia, ALL). AML affects myeloid cells, resulting in an abundance of abnormal immature cells within the blood-cell-producing bone marrow; normal hematopoietic processes become increasingly compromised. Persons with AML are more likely to have infections and have an increased risk of bleeding as the numbers of healthy blood cells decrease. [from MedlinePlus; https://www.nlm.nih.gov/medlineplus/ency/article/000542.htm ]
Approximately 10% of all leukemias harbor MLL1 translocations; more than 80 different partner genes in these fusions have been described. N-terminally truncated MLL1 alone is not sufficient to transform cells. (Winters and Bernt, 2017; pubmed:28232907)
Translocations with a breakpoint at 11q23 are found in many leukemias; these translocations involve the N-terminal part of the mixed lineage leukemia (MLL, now KMT2A) gene fused to >60 different partner genes. The two most common fusion partners are AF9 (now MLLT3) and AF4 (now AFF1). (Prange et al., 2017; pubmed:28114278)
KMT2A, lysine methyltransferase 2A, encodes a histone methyltransferase that methylates Lys-4 of histone H3 and plays an essential role in regulating gene expression during early development and hematopoiesis. H3 Lys-4 methylation represents a specific tag for epigenetic transcriptional activation; dysregulation of this methylation occurs in the development of many cancers. [Gene Cards, KMT2A; 2018.11.15]
MLLT3 encodes a component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase. [Gene Cards, MLLT3; 2018.11.15]
AFF1 encodes a protein that functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. [Gene Cards, AFF1; 2018.11.15]
MLLT10 has not been well characterized; it is thought to encode a protein involved in transcriptional regulation. [Gene Cards, MLLT10; 2018.11.15]
Many to one: 2 human to 1 Drosophila; the other human gene is MLLT6.
Many to one: 2 human to 1 Drosophila; the other human gene is KMT2B.
Many to one: 2 human to 1 Drosophila; the other human gene is MLLT1.
Many to one: 4 human to 1 Drosophila; the other human genes are AFF2, AFF3, AFF4.
