Clinical, Cytogenetic, and Molecular Findings in Two Cases of Variant t(8;21) Acute Myeloid Leukemia (AML)

Abstract

t(8;21)(q22;q22) is present in ~5-10% of patients with de novo acute myeloid leukemia (AML) and is associated with a better overall prognosis. Variants of the t(8;21) have been described in the literature, however, their clinical and prognostic significance has not been well-characterized. Molecular profiling of these cases has not previously been reported but may be useful in better defining the prognosis of this subset of patients. We present two cases of variant t(8;21) AML including clinical, cytogenetic, and molecular data.

Keywords: acute myeloid leukemia; core binding factor; cytogenetics; t(8;21); variant.

Figure 1

Abnormal cytogenetic and FISH findings in Patient #1. (A) Representative karyogram of an apparent t(8;21)(q22;q22) observed in 11 of 20 metaphases analyzed, unable to show submicroscopic small deletions due to cytogenetic technic limitation. The aberration was re-written as der(8)t(8;21)(q22;q22),der(21)del(8)(q22q22)t(8;21) based on FISH findings in (B,C). Arrows indicate aberrant chromosomes. Chromosome numbers are listed on the bottom. (B) Interphase FISH study using dual color dual fusion probes demonstrating an atypical pattern with one fusion signal for RUNX1-RUNXT1, one signal (red) for the RUINX1T1 locus, and two signals (green) for the RUNX1T1 locus. (C) Metaphase FISH study using dual color dual fusion probes demonstrating a derivative chromosome 8 [der(8)] carrying a fusion signal of RUNX1T1 and RUNX1, a derivative chromosome 21 [der(21)] carrying the green colored RUNX1 signal alone consistent with a sub-microscopic deletion of the rearranged 8q22 segment encompassing the 5′ RUNX1T1, a copy of a normal chromosome 8 [N(8)] and a copy of a normal chromosome 21 [N(21)].

Figure 2

Abnormal cytogenetic and FISH findings in Patient #2. (A) Representative karyogram of an apparent t(8;21)(q22;q22) observed in all of 20 metaphases analyzed, unable to show submicroscopic small deletions due to cytogenetic technic limitation. The aberration was re-written as der(8)t(8;21)(q22;q22),der(21)t(8;21)del(8)(q22q22) based on FISH findings in (B,C). Arrows indicate aberrant chromosomes. Chromosome numbers are listed on the bottom. (B) Interphase FISH study using dual color dual fusion probes demonstrating an atypical pattern with one fusion signal for RUNX1-RUNXT1, one signal (red) for the RUINX1T1 locus, and two signals (green) for the RUNX1T1 locus. (C) Metaphase FISH study using dual color dual fusion probes demonstrating a derivative chromosome 8 [der(8)] carrying a fusion signal of RUNX1T1 and RUNX1, a derivative chromosome 21 [der(21)] carrying the green colored RUNX1 signal alone consistent with a sub-microscopic deletion of the rearranged 8q22 segment encompassing the 5′ RUNX1T1, a copy of a normal chromosome 8 [N(8)] and a copy of a normal chromosome 21 [N(21)]. (D) Interphase FISH study using dual color dual fusion probes demonstrating a second atypical pattern with two signals (red) for the RUINX1T1 locus, three signals (green) for the RUNX1T1 locus and no fusion signal for RUNX1-RUNXT1.