title: inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman.
abstract: A 75-year-old woman presented with marked leukocytosis; the white cell count was 143.6 × 10³/μL with 38.6 % monocytes and 13.6 % immature granulocytes, including blasts. Bone marrow (BM) aspirate smears showed >90 % cellularity with hyperplasia of myeloid-lineage cells, 14.6 % monocytes, and 32.1 % blasts. The granulocyte series showed a range of dysplastic morphologies. The rate of peroxidase positivity was 51.5 %. CD36+ cells with monocytic differentiation comprised 64.6 % mononuclear cells. Metaphase spreads obtained from the BM revealed an aneuploid karyotype with -7 and a submetacentric marker chromosome derived from chromosome 2, which was determined to be inv(2)(p23q13) by fluorescence in situ hybridization using the Vysis ALK probe. RAN-binding protein 2 (RANBP2)-ALK fusion mRNA was confirmed by reverse transcriptase-mediated polymerase chain reaction and nucleotide sequencing. High-sensitivity anti-ALK immunohistochemistry of a BM biopsy specimen demonstrated nuclear membrane staining of leukemia cells. As the leukemia showed features of chronic myelomonocytic leukemia, the patient was treated with standard daunorubicin-cytarabine followed by azacitidine, leading to the durable suppression of leukemia progression. These findings suggest that inv(2)(p23q13)/RABBP2-ALK defines a small subset of myeloid leukemia characterized by differentiation to monocytes and sharing features of myelodysplastic syndrome/myeloproliferative neoplasm.
authors.affiliation: Department of Hematology, Tenri Hospital, 200 Mishima, Tenri, Nara, 632-8552, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Maesako
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Izumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okamori
authors.forename: Kayo
authors.initials: K
authors.lastname: Takeoka
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Kishimori
authors.forename: Atsuko
authors.initials: A
authors.lastname: Okumura
authors.forename: Gen
authors.initials: G
authors.lastname: Honjo
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001374:Azacitidine / Q000008:administration & dosage / Q000627:therapeutic use; D007446:Chromosome Inversion; D002889:Chromosomes, Human, Pair 2; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C000591371:RANBP2-ALK fusion protein, human; C094493:ran-binding protein 2; D003561:Cytarabine; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D001374:Azacitidine; D003630:Daunorubicin