title: Therapy-related acute myeloid leukemia 6 years after clonal detection of inv(11)(q21q23) and MLL gene rearrangement.
abstract: Results of recent studies with animal models suggest that expression of MLL fusion proteins promotes acute leukemogenesis. However, the most potent MLL fusion proteins are not sufficient for the development of acute myeloid leukemia (AML). The clinical data on the pathogenesis of this type of leukemia are limited. We analyzed the case of a patient with therapy-related AML with MLL rearrangement. The patient initially developed AML with t(8;21). Although the patient achieved complete remission with chemotherapy, an abnormal karyotype, inv(11)(q21q23), was detected. After 6-year persistence of a clone with the inversion 11 karyotype in the bone marrow, secondary AML developed. Results of fluorescence in situ hybridization analysis combined with magnet-activated cell sorting analysis showed that MLL rearrangement was detected in CD34+ and CD13+ fractions but not in a CD3+ fraction of the bone marrow. There were 2 important clinical findings. One was that MLL rearrangement was not sufficient for the development of leukemia. The other was that MLL rearrangement targets specific lineages.
authors.affiliation: Moriya Daiichi General Hospital, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takei
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Harumi Yamamoto
authors.initials: HY
authors.lastname: Mukai
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okoshi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoda
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagasawa
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D018826:CD13 Antigens / Q000096:biosynthesis; D007446:Chromosome Inversion / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D051788:Myeloid-Lymphoid Leukemia Protein; D018826:CD13 Antigens