| MN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | MN1 , MGCR, MGCR1, MGCR1-PEN, dJ353E16.2, meningioma (disrupted in balanced translocation) 1, MN1 proto-oncogene, transcriptional regulator, CEBALID | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 156100 MGI: 1261813 HomoloGene: 37620 GeneCards: MN1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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MN1 is a gene found on human chromosome 22, with gene map locus 22q12.3-qter. [5] Its official full name is meningioma (disrupted in balanced translocation) 1 because it is disrupted by a balanced translocation (4;22) in a meningioma.
MN1 is a transcription coregulator that enhances or represses gene expression through direct or indirect interaction with the gene regulatory machinery. Reported interactions include the BAF (SWI/SNF) complex. [6] RAC3 and p300. [7] MN1 can act as a coactivator of several transcription factors, including RAR/RXR and the vitamin D receptor. [8] In AML, MN1 binds to genomic sites enriched for binding motifs of ETS factors as well as hematopoietic transcription factors such as RUNX1, GATA2, HOXA cluster genes, and MEIS1. [6] MN1 induces a hematopoietic stem and progenitor gene expression program centered on HOXA cluster genes, particularly HOXA9 and MEIS1 via its interaction with the BAF complex [9] [6]
The translocation of MN1 was first reported in meningioma. [5] A substantial percentage of primitive neuro-ectodermal tumors (PNET) have MN1 translocations [10] Several different partners were described, although in many cases no fusion partner was identified. MN1 transloations also occur in up to 2% of acute myeloid leukemia (AML) [11] Described fusion partners include ETV6, STAT3 and FLI1. [12] [11] [13] About 50% of fusions are out of frame and result in high expression of MN1 via enhancer hijacking. [11] [6] High MN1 expression in AML and MDS is associated with poor outcome [14] [15] [16] [17] [18] [19] [20] [ excessive citations ]
Mutations in this gene have been associated with cleft palate [21] [22] [23] and an atypical form of rhombencephalosynapsis. [24]
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.
Acute promyelocytic leukemia is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARA) gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness, with a median survival time of less than a week. Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3, receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).
ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.
Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene.
Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene. The homologous protein in Drosophila is known as extradenticle, and causes changes in embryonic development.
CCAAT/enhancer-binding protein alpha is a protein encoded by the CEBPA gene in humans. CCAAT/enhancer-binding protein alpha is a transcription factor involved in the differentiation of certain blood cells. For details on the CCAAT structural motif in gene enhancers and on CCAAT/Enhancer Binding Proteins see the specific page.
Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.
Pre-B-cell leukemia transcription factor 2 is a protein that in humans is encoded by the PBX2 gene.
PR domain containing 16, also known as PRDM16, is a protein which in humans is encoded by the PRDM16 gene.
C-type lectin domain family 12 member A is a protein that in humans is encoded by the CLEC12A gene.
Biphenotypic acute leukaemia (BAL) is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage".
Minimally differentiated acute myeloblastic leukemia is a subtype of AML. It is classified as M0 by FAB. It represents 2–3% of all cases of AML. Although minimally differentiated AML was recognized earlier, criteria for FAB M0 were developed in 1987. The blasts in these cases cannot be recognized as myeloid based on morphology and cytochemistry, but immunophenotyping demonstrates myeloid antigens.
Tet methylcytosine dioxygenase 2 (TET2) is a human gene. It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies.
AI-10-49 is a small molecule inhibitor of leukemic oncoprotein CBFβ-SMHHC developed by the laboratory of John Bushweller with efficacy demonstrated by the laboratories of Lucio H. Castilla and Monica Guzman. AI-10-49 allosterically binds to CBFβ-SMMHC and disrupts protein-protein interaction between CBFβ-SMMHC and tumor suppressor RUNX1. This inhibitor is under development as an anti-leukemic drug.
