MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia withthe t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with Fanconi anemia

We describe a boy with Fanconi anemia (FA) who developed acute lymphoblasti c leukemia (ALL) (FAB-L I) followed by acute myeloid leukemia (AML) (FAB-M5 ) at relapse. The patient was diagnosed with early pre-B-cell ALL without p receding aplastic anemia and was treated with ALL-oriented chemotherapy whi ch included doxorubicin (a total dose of 140 mg/m(2) administered), which i s a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,X Y, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL ge ne rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in AL L. A diagnosis of FA was confirmed by an increased number of chromosomal br eaks and rearrangements in peripheral blood lymphocytes cultured with mitog en in the presence of mitomycin C. We conclude that this FA patient develop ed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP f usion. Further examination of such patients would shed light on leukemogene sis in FA patients. (C) 2000 Wiley-Liss, Inc.