The MECOM locus is located on the long arm of chromosome 3 at position 3q26.2 . It includes several alternative transcripts, with EVI1 being a prominent oncogenic zinc-finger transcription factor. EVI1 is known for its role in myeloid malignancies, where its overexpression contributes to disease progression and poor clinical outcomes .
EVI1 exists in two main forms:
EVI1 contains ten zinc fingers arranged in two sets: seven in the N-terminal and three in the C-terminal. These zinc fingers allow EVI1 to bind DNA and regulate gene expression .
The MDS1-EVI1 (ME) isoform is critical for the long-term function of hematopoietic stem cells (HSCs). Studies have shown that ME is exclusively expressed in the stem cell compartment and is essential for maintaining the quiescence and long-term repopulation capacity of HSCs . ME deficiency leads to a reduction in HSC numbers and a shift from quiescence to active cycling, which can result in hematopoietic defects .
The dysregulation of EVI1 is strongly associated with leukemogenesis. Overexpression of EVI1 is linked to poor outcomes in myeloid malignancies, including acute myeloid leukemia (AML). The oncogenic properties of EVI1 are attributed to its ability to disrupt normal gene expression and promote uncontrolled cell proliferation .
Understanding the biology of MECOM and its associated transcripts has significant implications for developing targeted therapies. Current research is focused on identifying novel therapeutic interventions that can modulate EVI1 activity and improve clinical outcomes for patients with myeloid malignancies .