MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies

The Ecotropic Viral Integration Site 1 gene (EVI1), also known as the MDS1 and EVI1 Complex Locus (MECOM), is located on chromosome 3q26.2. Extensive studies have implicated this gene's role in maintaining and replicating normal hematopoietic stem cells, as well as its role as an oncogene when aberrantly expressed. Translocations involving the MECOM gene at 3q26.2 are well-documented and characterized in myeloid disorders, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelogenous leukemia (CML), and is associated with a poor prognosis. Recently, cases of MECOM rearrangements and activation have also been documented in lymphoid malignancies, including acute lymphoblastic leukemia (ALL) and persistent polyclonal binucleated B-cell lymphoma (PBBL). A review of the literature reveals four confirmed cases of MECOM cytogenetic abnormalities in lymphoid disorders, each of which could potentially implicate MECOM in the development or transformation of lymphoid disease. In two cases, a B-cell ALL (B-ALL) case and a T-cell non-Hodgkin's lymphoma case, the MECOM aberration was the sole abnormality, suggesting that it may have an important role in the development of the disease. In the other two cases, a case of 5q- syndrome and a case of plasma cell myeloma, both acquired a MECOM aberration as the cases transformed to ALL, potentially implying that it has a role in ALL disease transformation. There were also 82 cases of PBBL with inv(3) in particular as the MECOM abnormality of interest. In the literature, there were also mentions of at least 38 other cases of MECOM aberrant activation, but these cases may or may not involve 3q26.2 rearrangement. MECOM overexpression may also develop independently of any chromosomal rearrangement, with other possible pathways involved. A query of the Mitelman Database of Chromosomal Aberrations and Gene Fusions in Cancer revealed another 12 cases where 3q26 rearrangements were reported in lymphoid malignancies, but none of these studies performed fluorescence in-situ hybridization (FISH) to confirm or deny the presence of a MECOM rearrangement. Recent findings also demonstrate that MECOM may also play an important role in lymphoid leukemogenesis, progression, and transformation, although it may be in a manner distinct from that in myeloid malignancies. Overall, MECOM still needs to be further characterized and investigated in the context of lymphoid malignancies as a potential biomarker and therapeutic target.