title: Terminal differentiation in vitro of patient-derived post-TMD megakaryoblastic AML cells.
abstract: Differentiation induction is a therapeutic principle in acute promyelocytic leukemia (AML) using all- trans retinoic acid. In cell lines with properties of AML M6/M7 (K562 and CMK), differentiation towards megakaryopoietic and erythropoietic phenotypes can be induced in vitro. Transitory myeloproliferative disorder (TMD) is a self-limited disorder of newborn infants with Down syndrome, phenotypically resembling acute myeloid leukemia of megakaryoblastic lineage. Despite spontaneous disappearance of blasts from blood and bone marrow, in about 10% of the patients, overt acute megakaryoblastic leukemia (AML M7) develops up to 4 years later. Recently, mutations of the GATA1 transcription factor have been identified in the megakaryoblastic leukemia of Down syndrome. Here, we studied cells from a patient suffering from megakaryoblastic AML at the age of 2.5 years after spontaneous remission of neonatal TMD. In vitro, terminal differentiation towards a megakaryocyte-like phenotype could be induced by phorbol myristate acetate (PMA), with typical morphological features, upregulation of platelet-specific and downregulation of erythroid antigens, going along with downregulation of c-myc. Whether spontaneous resolution of TMD is a process due to terminal differentiation is still open; however, here we give evidence that in vitro differentiation can be induced even in blasts deriving from an overt AML French-American-British (FAB) M7 after TMD.
authors.affiliation: University Children's Hospital Ulm, Prittwitzstrasse 43, 89070, Ulm, Germany. carl.classen@medizin.uni-ulm.de.
authors.forename: C F
authors.initials: CF
authors.lastname: Classen
authors.affiliation: First Clinic for Children and Adolescents, Klinikum Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gnekow
authors.affiliation: University Children's Hospital Ulm, Prittwitzstrasse 43, 89070, Ulm, Germany.
authors.forename: K-M
authors.initials: KM
authors.lastname: Debatin
mesh_terms: D000208:Acute Disease; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D005434:Flow Cytometry; D006021:Glycophorins / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000473:pathology*; D008533:Megakaryocytes / Q000502:physiology; D009196:Myeloproliferative Disorders / Q000150:complications*; D010641:Phenotype; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D006021:Glycophorins; D040201:Platelet Membrane Glycoprotein IIb; D013755:Tetradecanoylphorbol Acetate