title: Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples.
abstract: Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells had chromosome 13q deletions, and the secondary myelofibrosis (SMF) cells had JAK2V617F mutations. The myelofibrosis patient cell-derived iPS (MF-iPS) were confirmed as possessing these parental disease-specific genomic markers. The capacity to form three germ layers was confirmed by teratoma assay. By co-culture with specific feeder cells and cytokines, MF-iPS can re-differentiate into blood progenitor cells and finally into megakaryocytes. We found that mRNA levels of interleukin-8, one of the candidate cytokines related to the pathogenesis of myelofibrosis, was elevated predominantly in megakaryocytes derived from MF-iPS. Because megakaryocytes from myelofibrosis clones are considered to produce critical mediators to proliferate fibroblasts in the bone marrow and iPS can provide differentiated cells abundantly, the disease-specific iPS we established should be a good research tool for this intractable disease.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Hosoi
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Taoka
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Arai
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kamikubo
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Takayama
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Eto
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Tokyo, Japan. Electronic address: kurokawa-tky@umin.ac.jp.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020125:Mutation, Missense; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013724:Teratoma
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C507924:JAK2 protein, human; D053614:Janus Kinase 2