Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study.

Multicolor fluorescence in situ hybridization (M-FISH) was performed on bone marrow cells of 116 unselected cases of therapy-related myelodysplasia (t-MDS) or acute myeloid leukemia (t-AML), and the results were compared with those of previously performed with G-banding. Among 18 patients with a normal karyotype, no cryptic chromosome aberrations were observed with M-FISH. In 56 patients with a previously solved abnormal karyotype, only 17 new aberrations were identified, whereas 153 new aberrations were detected by M-FISH in 42 patients with a previously unsolved karyotype. In total, 112 of the new aberrations were unbalanced translocations, and only nine were balanced translocations. A clustering of breakpoints was observed in the centromeric or pericentromeric region of chromosomes 1, 5, 7, 13, 17, 21, and 22 in 48 of 98 patients with t-MDS and t-AML and an abnormal karyotype, and was related to previous therapy with alkylating agents. In seven of eight patients with chromosome derivatives containing material from three or more chromosomes or having sandwichlike chromosomes, those made up of several small interchanging layers of material from two chromosomes showed mutations of TP53. M-FISH had little impact on the prognostic classification of t-MDS and t-AML, as only three patients changed prognostic groups as a result of M-FISH.