MECOM (EVI1) Rearrangements: A Review and Case Report of Two MDS Patients with Complex 3q Inversion/Deletions

Acute myelogeneous leukemia (AML) with inv(3)/t(3;3)(q13q25) is associated with aberrant expression of the stem-cell regulator MECOM (aka EVI1). Two bone marrow samples received in the OHSU Knight Diagnostic Laboratories (KDL) Cytogenetics Laboratory for chromosomes and FISH for a question of progression of myelodysplastic syndrome (MDS) to AML showed complex abnormalities including a deletion of chromosome 3q, one with del(3)(q13q25) and the other with del(3)(q22q25). In light of the prognostic importance of the activation of the MECOM oncogene and the concurrent inactivation of the GATA2 tumor suppressor that occurs with the classic inversion of chromosome 3q, fluorescence in situ hybridization (FISH) was performed using two different probe designs to better define the 3q deletions in the two cases. Using the Abbott Molecular Laboratories dual fusion MECOM/RPN1 probe, interphase and metaphase cells in both patients showed a variant single fusion (orange/green/fusion) signal pattern consistent with fusion and deletion. Using the three-color (red/green/aqua) Cytocell EVI1 probe, interphase cells in both cases showed a split red/green signal with the aqua signal remaining with the green signal. The distance between the split signals was generally less than is usually seen in the commonly described inverted chromosome 3. These findings are therefore consistent with a complex inversion and concurrent deletion/deletions of chromosome 3q. Thus, the deletion 3q seen in G-banded chromosomes from bone marrow from these two patients is most consistent with the activation of MECOM and the inactivation of GATA2.