KMT2A

Overview of the KMT2A gene and its significance in human biology

KMT2A Gene

The KMT2A gene, also known as MLL (Mixed-Lineage Leukemia), is a crucial gene located on chromosome 11q23.3. It encodes a protein that functions as a histone methyltransferase, which is essential for the regulation of gene expression through chromatin modification. The KMT2A protein plays a significant role in the regulation of gene expression, cell cycle, and developmental processes.

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Histone methylation is a key process regulated by KMT2A.

Function

The KMT2A protein is part of a large multiprotein complex that specifically methylates histone H3 at lysine 4 (H3K4). This methylation is a marker of active chromatin and is associated with transcriptional activation. The KMT2A complex is involved in the regulation of homeobox (HOX) genes, which are critical for embryonic development and hematopoiesis.

Clinical Significance

Mutations and translocations involving the KMT2A gene are implicated in various forms of leukemia, particularly acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). These genetic alterations often result in the formation of fusion proteins that disrupt normal gene regulation, leading to uncontrolled cell proliferation.

Leukemia

Translocations involving KMT2A are found in approximately 5-10% of acute leukemias. The most common translocation is t(4;11)(q21;q23), which results in the fusion of KMT2A with the AF4 gene. This fusion protein acts as an aberrant transcription factor, driving the expression of genes that promote leukemogenesis.

Leukemia cells often exhibit chromosomal translocations involving KMT2A.

Research and Therapeutic Approaches

Research into the KMT2A gene and its associated pathways is ongoing, with the aim of developing targeted therapies for leukemias involving KMT2A translocations. Strategies include the use of small molecule inhibitors that target the KMT2A fusion proteins or their downstream signaling pathways.

Related Pages

• Histone methylation
• Chromatin remodeling
• Acute lymphoblastic leukemia
• Acute myeloid leukemia
• Gene expression regulation