CALM-AF10 fusion induces chromosomal instability. (A) Hypomethylated cells display increased chromosomal instability. T-REx-293 cells expressing CALM-AF10 (H3K79 hypomethylation) or CALM-AF10ΔOM-LZ (normal H3K79 methylation) were irradiated at 2 Gy, and the average number of chromosome breaks (left panel) and chromosome gaps (right panel) per metaphase spread was determined 1 hour after irradiation. (B) CALM-AF10–positive patients show more additional cytogenetic abnormalities than patients with an MLL-AF9 or a PML-RARA fusion. Percentages of cases with a secondary (one additional rearrangement to the primary translocation) and complex (2 or more additional rearrangements) cytogenetic abnormalities were calculated. (C) Model for chromosomal instability in association with CALM-AF10 translocations.