title: Deletion 6p23 and add(11)(p15) leading to NUP98 translocation in a case of therapy-related atypical chronic myelocytic leukemia transforming to acute myelocytic leukemia.
abstract: A NUP98 gene translocation occurring with a del(6p23) and an add(11)(p15) was determined in a 61-year-old patient with therapy-related atypical chronic myelocytic leukemia after complete remission from acute promyelocytic leukemia that eventually underwent clonal evolution and transformed to CD56-positive acute myelocytic leukemia (French-American-British classification M0). Precise chromosome analysis by G-banding, spectral karyotyping analysis, and dual-color fluorescence in situ hybridization showed this abnormality as 46,XY,del(6)(p23),add(p15). ish del(6)(NUP98-,D6Z1+),der(7)(NUP98+,D7Z1+),der(11)(NUP98+,D11Z1). A split signal of NUP98 was observed in 68.4% of the 117 cells analyzed, which clearly indicated that the NUP98 partially translocated to chromosome 7. However, the potential fusion partner of the NUP98 was not HOX family or DEK. The fusion gene has not been found by a differential display method. The significance of simultaneously combined del(6)(p23), which also has been reported with secondary leukemogenesis, has not been elucidated. Additional karyotype abnormalities evolved increasingly, and leukocytosis with blasts with more complex karyotypic abnormalities appeared 5 months later. Careful and continuous analysis of karyotype change clarified the process of the clonal evolution after NUP98 translocation. Further investigation of molecular characterization of this NUP98 translocation and interaction with 6p23 abnormalities might be worthwhile for understanding leukemogenesis.
authors.affiliation: Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, 431-3192, Japan. akihirot@hama-med.ac.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeshita
authors.forename: Kensuke
authors.initials: K
authors.lastname: Naito
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinjo
authors.forename: Naohi
authors.initials: N
authors.lastname: Sahara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsui
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Beppu
authors.forename: Kaori
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Horii
authors.forename: Masato
authors.initials: M
authors.lastname: Maekawa
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
mesh_terms: D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human