Core binding factor (CBF) leukemias represent an important prognostic group in acute myeloid leukemia (AML). The t(8;21)(q22;q22)/RUNX1 -RUNX1T1 is one of the most frequent abnormalities in childhood AML (7–16%) and is related to a good prognosis. However, on rare occasions, an additional chromosome may be involved in this translocation, which may result in a poor clinical outcome for the patient. In this sense, the prognostic value of the RUNX1 -RUNX1T1 fusion has been widely discussed in the literature. Approximately 3–4% of AML cases with t(8;21)/RUNX1 -RUNX1T1 occur in the context of complex rearrangements, with only a few cases reported in children (0.05–1.1%). Our aim in this work is to demonstrate the clinical and molecular data from four AML pediatric patients with variant three-way translocations t(8;V;21), characterizing in detail the extra chromosomes and fusion products.

In our cohort of 146 children diagnosed with AML, we observed 22 with complex karyotypes (>3 abnormalities). To date, we detected the t(8;21) in 5/22 cases, among which 4 patients presented the involvement of a third chromosome in t(8;21), characterizing variant three-way translocations t(8;V;21). To characterize the patient's karyotypes, G-banding, FISH, and high-resolution molecular cytogenetics experiments (PCP, WCP, M-FISH, and MCB) were performed on bone marrow and/or peripheral blood cells under standard protocols.

Regarding the mechanism of this type of translocation, Downing et al. (1993) and Tanaka et al. (2012) reported that there are at least two stages for the formation of such complex variants. The region 21(q22) (harboring the RUNX1 gene) translocates to the long arm of chromosome 8, while region 8q22 (harboring the RUNX1T1 gene) translocates to a third chromosome. Interestingly, in our 4 cases, t(8;V;21) demonstrated the same biological behavior in the rearrangement as the other cases reported in the literature. Although, unlike the cases previously reported in the literature, the karyotypes characterized in our study were cryptic, reaffirming the importance of an accurate diagnosis of RUNX1 -RUNX1T1 fusion products.

With our approach by molecular cytogenetic techniques, we were able to precisely define the breakpoints of the three-way translocations, which will be of importance for future studies, investigating putative genes with impact on the genesis of pediatric CBF leukemias.