A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene.
We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA.
Department of Clinical Laboratory, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Tomoe
T
Kikuma
Department of Clinical Laboratory, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. nakamati@med.kobe-u.ac.jp.
Yuji
http://orcid.org/0000-0002-1648-0606
Y
Nakamachi
Department of Clinical Laboratory, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Yoriko
Y
Noguchi
Department of Clinical Laboratory, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Yoko
Y
Okazaki
Department of Clinical Pathology, Tenri Hospital, Tenri, Nara, Japan.
Daisuke
D
Shimomura
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Kimikazu
K
Yakushijin
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Katsuya
K
Yamamoto
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Hiroshi
H
Matsuoka
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Hironobu
H
Minami
Division of Diagnostic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Tomoo
T
Itoh
Division of Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Seiji
S
Kawano
D002466:Cell Nucleolus / Q000473:pathology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000473:pathology / Q000648:ultrastructure; D005091:Exons / Q000235:genetics; D050939:Gene Fusion; D042381:Granulocyte Precursor Cells / Q000166:cytology; D006801:Humans; D060828:Induction Chemotherapy; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023981:Sarcoma, Myeloid / Q000175:diagnosis / Q000628:therapy; D014212:Tretinoin / Q000627:therapeutic use
D002843:Chromatin; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000090243:Nucleophosmin; D014212:Tretinoin
Acute promyelocytic leukemia; All-trans retinoic acid; Myeloid sarcoma; NPM1/RARA; t(5;17)(q35;q12–21)