title: Secondary near-tetraploidy with double der(15)t(15;17) in acute promyelocytic leukemia in relapse.
abstract: Tetraploidy or near-tetraploidy is a rare cytogenetic abnormality in acute myelocytic leukemia. We report here a case of acute promyelocytic leukemia that showed near-tetraploidy with double der(15)t(15;17) the leukemia relapsed. At diagnosis, cytogenetic analysis failed to reveal any karyotypic abnormality; however, a promyelocytic leukemia-retinoic acid receptor alpha (PML/RARA) fusion transcript of the bcr3-type was detected with reverse transcriptase-polymerase chain reaction analysis, and a single PML/RARA fusion signal was observed with fluorescence in situ hybridization analysis. At the first relapse, the majority of leukemic cells showed pseudodiploid karyotypes with der(15)t(15;17), as well as additional chromosomal abnormalities, and exhibited a single PML/RARA fusion signal. A small fraction of leukemic cells, however, showed near-tetraploid karyotypes with double der(15)t(15;17), as well as some additional chromosomal abnormalities in common with the pseudodiploid clones, and exhibited double PML/RARA fusion signals. At the second and third relapses, leukemic cells with near-tetraploidy and double PML/RARA fusion signals became predominant. The PML/RARA fusion transcript of the bcr3 type was also observed at each relapse. In addition, Southern blot analysis of the RARA gene at diagnosis and at the second relapse showed a common rearranged band. Notably, giant, bizarre, and hypogranular promyelocytes expressing CD2, CD34, and HLA-DR appeared at the first relapse and became predominant at the second and third relapses. These observations indicate that the APL cells with near-tetraploidy and double der(15)t(15;17) clonally evolved from the pseudodiploid leukemic cells and exhibited the bizarre morphology and aberrant surface immunophenotypes.
authors.affiliation: Department of Hematology and Oncology, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Morita
authors.forename: Asami
authors.initials: A
authors.lastname: Takahashi
authors.forename: Koh
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Miki
authors.forename: Naomi
authors.initials: N
authors.lastname: Murakami
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
mesh_terms: D015139:Blotting, Southern; D001854:Bone Marrow Cells; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011123:Polyploidy; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic