title: Terminal deletion of the long arm of chromosome 9 in acute promyelocytic leukemia with a cryptic PML/RAR alpha rearrangement.
abstract: Deletions of the long arm of chromosome 9 (9q-) are rare aberrations specifically found in acute myeloid leukemia (AML). Here we describe the first case of acute promyelocytic leukemia (APL) with a terminal 9q deletion as a sole abnormality. Chromosome analysis of the bone marrow cells showed 46,XX,del(9)(q22) in all 20 metaphases. Fluorescence in situ hybridization (FISH) analysis with painting probes of chromosomes 15, 17, and 9 revealed only two normal chromosomes 15 and 17, normal chromosome 9, and del(9)(q22). FISH with cosmid DNA probes flanking the breakpoints of t(15;17) did not show the retinoic acid receptor alpha (RAR alpha)/PML fusion signal usually generated on the der(17) t(15;17). However, rearrangement of the RAR alpha gene and expression of the PML/RAR alpha chimeric transcript were identified by Southern blot and reverse transcriptase-polymerase chain reaction analyses, respectively. These results suggested that the PML/RAR alpha fusion gene was generated by submicroscopic interstitial insertion of the RAR alpha gene into the PML gene. Therefore, 9q- was interpreted as a secondary aberration following the PML/RAR alpha rearrangement. The patient died during induction therapy because of intracerebral hemorrhage. Considering other reported cases of APL with 9q-, 9q- may be an adverse prognostic factor in APL as observed in AML with t(8;21).
authors.affiliation: Department of Hematology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsurukubo
authors.forename: K
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein