title: JAK2V617F-positive essential thrombocythemia and multiple myeloma with IGH/CCND1 gene translocation coexist, but originate from separate clones.
abstract: Overlapping of essential thrombocythemia (ET) and multiple myeloma (MM) has been extremely rare. Our report concerns a case with concomitant ET and MM, where JAK2V617F was present in non-myeloma peripheral blood leukocytes and bone marrow (BM) hematopoietic cells, but not in BM-derived CD138-positive myeloma cells. In contrast, double-color fluorescence in situ hybridization analysis showed that BM-derived CD138-positive myeloma cells possessed the gene translocation between the immunoglobulin heavy chain gene and the cyclin D1 gene, which was not involved in non-myeloma hematopoietic cells. This is the first case with concomitant ET and MM in which the 2 hematologic neoplasms were shown to have originated from separate malignant clones at hierarchically different differentiation levels resulting from independent acquisition of different molecular aberrations. Among the 10 reported cases, including ours, ET preceded MM in 8 cases, but MM never preceded ET. We suggest that MM clones may have greater proliferative potency compared with ET clones, and that the treatment modification from ET to MM did not seem to exacerbate ET in most reported cases, perhaps because of the suppression of the ET clone by both the cytotoxic effect of anti-myeloma therapy and the clonal repression by MM progression.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. junkuro@koto.kpu-m.ac.jp
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Ruriko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kurita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shimizu
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horiike
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D053668:Syndecan-1 / Q000378:metabolism; D013921:Thrombocytopenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: C530104:CCND1 protein, human; D007143:Immunoglobulin Heavy Chains; C508241:SDC1 protein, human; D053668:Syndecan-1; D019938:Cyclin D1; C507924:JAK2 protein, human; D053614:Janus Kinase 2