Detection of E2A translocations in leukemias via fluorescence in situ hybridization

Three rearrangements in ALL disrupt E2A and create E2A fusion proteins: the t(1;19)(q23;p13) and ESA-PBX1, t(17;19)(q22;p13) and E2A-HLF and a cryptic inv(19)(p13;q13) and E2A-FB1, While E2A is fused to PBX1 in most ALLs with a 1(1;19), 5-10% of cases have translocations that appear identical, but d o not affect E2A or PBX1. Because more intensive therapy improves the outco me of patients with E2A-PBX1(positive) (1;19) translocations, it is critica l to identify this subset of patients so that appropriate therapy can be ad ministered. In addition, there are balanced and unbalanced variants of the 1(1;19) and controversy exists regarding the clinical significance of this distinction. We have developed a two-color fluorescence in situ hybridizati on assay that accurately detects E2A translocations in metaphase and interp hase cells, distinguishes between balanced and unbalanced variants and iden tifies patients with a 1(1;19) who lack E2A-PBX1 fusion, We found that clon al microheterogeneity is common in patients with E2A translocations and mos t patients have mixtures of cells with balanced and unbalanced translocatio ns, suggesting that this distinction represents two ends of a continuum rat her than distinct biological entities. These reagents should have widesprea d clinical utility and be useful for translational and basic research studi es involving E2A translocations and this region of chromosome 19p13.