A New Complex Translocation T(8;11;21)(Q22;Q24;Q22) In Acute Myeloid Leukemia With Runx1/Runx1t1

The t(8;21)(q22;q22) translocation involving RUNX1 at 21q22 and RUNX1T1 at 8q22 is found in 10% of cases of acute myeloid leukemia (AML) M2 subtype. This translocation results in the formation of a RUNX1/RUNX1T1 fusion gene, which contributes to leukemic transformation by transcriptional repression of normal RUNX1 target genes, on der (8)t(8;21)(q22;q22). AML with t(8;21) is usually associated with a good response to chemotherapy and long-term diseasefree survival. It has been reported that variant translocations, the majority of which are complex three-way translocations, occur in approximately 3 to 4% of cases of AML with t(8; 21). However, clinical and hematological features of AML with variant t(8;21) remain to be completely characterized. Here, we describe a new complex translocation t(8;11;21) (q22;q24;q22) in a case of AML with RUNX1/RUNX1T1. A 62-year-old man was admitted because of anemia and thrombocytopenia. He had no history of chemotherapy or radiotherapy. Peripheral blood analysis showed hemoglobin 7.8 g/dL, platelets 33 × 10/L, and leukocytes 4.6 × 10/L with 14% myeloblasts. Bone marrow was hypercellular with 18.2% myeloblasts, 60.0% mature myeloid cells, 5.6% eosinophils, 4.4% monocytes, 6.6% lymphocytes, and 2.6% erythroblasts. Myeloblasts had Auer rods and a few azurophilic granules in the basophilic cytoplasm. Myeloid dysplasia including the pseudo-Pelger-Huët anomaly was also found (Fig. 1A). Myeloblasts were positive for myeloperoxidase staining and immunophenotypically positive for CD13, CD19, CD33, CD34, CD56, and HLA-DR. In light of the cytogenetic and genetic abnormalities described below, we made a diagnosis of AML with RUNX1/RUNX1T1 according to the World Health Organization classification. Initial induction therapy with cytarabine and idarubicin failed, but the patient achieved hematological and cytogenetic complete remission (CR) after re-induction therapy with cytarabine and daunorubicin. The residual myeloblasts were negative for CD19 and CD56 after the attainment of CR. He received a further three courses of consolidation therapy with high-dose cytarabine, and remained in molecular CR for more than 10 months. G-banding analysis of bone marrow cells at diagnosis showed 46, XY, t (8;11;21) (q22; q24; q22) [20] (Fig. 1B). Spectral karyotyping confirmed three derivative chromosomes: der(8)t(8;21)(q22;q22), der(11)t(8;11)(q22;q24), and der(21)t(11;21)(q24;q22) (Fig. 1C). Fluorescence in situ hybridization (FISH) on metaphase spreads detected the RUNX1/RUNX1T1 fusion signal on the der (8) t (8;21) (q22; q22) (Fig. 1D). Reverse-transcription polymerase chain reaction also confirmed the RUNX1/RUNX1T1 fusion transcript. We have presented a complex three-way translocation t(8; 11;21)(q22;q24;q22) and detected the RUNX1/RUNX1T1 fusion gene in a patient with AML. In the Mitelman database, four AML M2 cases with t (8;11; 21) involving 8q22 and 21q22 have been described (Table 1). Their breakpoints in chromosome 11 were clustered to 11p15 (two cases) and 11q13 (two cases). Thus, to our knowledge, this is the first case with a complex t(8;21) translocation involving the breakpoint 11q24. With regard to breakpoints in other chromosomes, Kim et al. summarized 24 adult cases of AML with variant t(8;21), and demonstrated that there was no overlap of breakpoints in the involved chromosomes, except for 20p13 (two cases). Thus, there seem to be few recurrent breakpoints involved in variant t(8;21). The t(8;11;21)(q22;q24;q22) translocation generated only the RUNX1/RUNX1T1 fusion gene on the der(8)t(8;21)(q22;