A new classification of interphase nuclei based on spatial organizations of chromosome 8 and 21 for t(8;21) (q22;q22) acute myeloid leukemia by three-dimensional fluorescence in situ hybridization

•We studied spatial organizations of chromosome 8 and 21 for AML-M2 by 3D-FISH.•Nuclei were classified into normal, transitional, and malignant nuclei.•Occurrences of each type nuclei were associated with the disease progression.•d/R of chromosome 8 was similar to d/R of chromosome 21 for relapse sample.•Centers of close chromosomal pairs were more internal than normal pairs.

Interphase heterogenous chromosomes spatially close to each other are predominantly located near the center of nuclei and are prone to incur translocations. We screened a t(8;21) (q22;q22) acute myeloid leukemia-M2 patient during three phases (post-chemotherapy, remittent stage, and relapse) and a donor of normal karyotype as control by two-(2D) and three-dimensional (3D)-fluorescence in situ hybridization (FISH). Our classification of nuclei (normal, transitional, and malignant nuclei) by 3D-FISH analyses may provide a more precise prognosis than 2D-FISH results, especially for remittent stage sample in our study, in which 2D-FISH findings showed normal results, whereas 3D-FISH results showed extreme abnormalities (normal nuclei 27%, transitional nuclei 36%, malignant nuclei 37%). The relative radial positions (d/R) of chromosomes 8 were similar to d/R of chromosomes 21 for the relapse sample. We classified heterogenous chromosome pairs into close pairs and normal pairs based on their relative distances (d′/(2R)). The centers of close pairs were more internal than normal pairs in nuclei in all samples, and the d/R values of a given-type pairwise heterogenous chromosomes were similar among four samples. Our data demonstrate that the classification of nuclei based on spatial organization of chromosomes by 3D-FISH is reasonable and essential for evaluating acute myeloid leukemia prognosis.