Acute myeloid leukemia (M2) with a cryptic RUNX1/RUNX1T1 t(1;21;8)(p36;q22;q22) variant.

Fig. 1. G-banded karyogram from the patient’s bone marrow. Arrows indicate a t(1;8)(p36;q22). The t(8;21) translocation occurs in 5e12% of acute myeloid leukemia (AML) cases, often occurring in the younger population. This translocation fuses the RUNX1 gene (previously AML1) on chromosome band 21q22 to the RUNX1T1 (previously known as ETO) on 8q22, resulting in a RUNX1/RUNX1T1 hybrid transcript on the derivative chromosome 8 [1,2]. According to the World Health Organization, this type of AML is associated with a favorable prognosis [1]. Variant translocations account for approximately 3e4% of all AML-M2 with RUNX1/ RUNX1T1 fusion transcripts [3], and the clinical consequences of such variants are less clearly defined. Here, we present a case of AML-M2 with a cryptic three-way translocation, t(1;21;8)(p36;q22;q22). In January 2009, a 45-year-old African-American man presented with a 2-week history of shortness of breath, fever, chills, and gum bleeding. No lymphadenopathy, organomegaly, or petechiae were noted. Complete blood count revealed an elevated white blood cell count, at 11.1 10/L with 69% blasts, 20% segmented cells, 5% bands, 4% lymphocytes, and 2% monocytes. The hemoglobin was decreased, at 8.1 g/L, and the platelet count was also low, at 37 10/L. The morphologic and immunophenotypic features of the bone marrow aspirate and core biopsy were indicative of an expanded population of aberrant myeloid blasts (CD45þ, CD34þ, CD117þ, HLA-DRþ, CD13þ, CD33þ, CD15þ, CD19þ and CD56þ, MPOþ and negative for nonspecific esterase), overall consistent with AML. Expression of CD19, however, suggested the possibility of AML with t(8;21). Cytogenetic study of the bone marrow cells revealed the karyotype (described according to ISCN 2005 [4]) as 46,XY,t(1;8)(p36;q22)[19]/46,XY[1] (Fig. 1). Because these results were inconsistent with the morphologic and immunophenotypic reports, FISH analysis was performed using the Vysis LSI AML1/ETO dual-color, dual-fusion translocation probe (Abbott Molecular, Des Plaines, IL). A single RUNX1/RUNX1T1 fusion product was detected on the derivative chromosome 8, a small signal of RUNX1T1 at band 1p36 on chromosome 1, a normal RUNX1T1 signal in the normal homolog 8, a normal RUNX1 signal on the normal copy of chromosome 21, and a small RUNX1 signal on the second copy of chromosome 21 (Fig. 2).