Morphological and cytogenetic changes in therapy-related leukemia developed in a t(8;21)-acute myeloid leukemia (M2) patient: Sequential cytogenetic and molecular analyses

A patient with acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22) achiev ed complete remission with remission-induction chemotherapy followed by con solidation and intensification chemotherapies. T(8;21)(q22;q22) disappeared , but chimeric AML1/MTG8 was continuously detected in bone marrow cells. Fo llowing the development of therapy-related leukemia after 1 year, evolution of therapy-related AML-M4 with t(11;17)(q23;q25) and the rearrangement of the MLL gene were observed, while AML/MTG8 disappeared. After reinduction a nd following intermittent chemotherapies, a subsequent alternative transfor mation to AML-M2 occurred after detection of t(3;21)(q21;q22), with a break in the AML1 gene shown by interphase fluorescence in situ hybridization an alysis. This leukemia transformed to AML-M4 after t(9;22)(q34;q11), with a minor BCR/ABL rearrangement, and then finally to AML-M2. This therapy-relat ed leukemia was resistant to chemotherapy. These findings indicate that alt erations in cytogenetic and molecular events caused by chemotherapeutic age nts contribute to the sequential evolution of new leukemic clones with diff erent morphology. Int J Hematol. 2000;71:353-358. (C) 2000 The Japanese Soc iety of Hematology.