title: Delayed processing of bone marrow samples reveals a prognostic pattern of NME mRNA expression in cytogenetically normal acute myeloid leukemia.
abstract: Improvements in the therapy of cytogenetically normal acute myeloid leukemia (CN-AML) will depend largely on the characterization of functional subtypes identified by prognostic markers. Exposing leukemic cells to stress ex vivo may reveal relevant phenotypic markers not apparent in freshly explanted cells. Here, we assess the prognostic relevance of expression of the nucleoside diphosphate kinase genes NME1 and NME2 in a cohort of 78 patients with CN-AML aged < 60 years using archived mononuclear cell samples originally prepared from bone marrow either directly (n = 25) or following 2-3 days of transport (n = 53). The stress conditions arising during transport resulted in the development of a prognostic pattern of NME mRNA with maintenance of high NME2 mRNA being a strong indicator of increased event-free survival independent of FLT3-internal tandem duplication. Prospective analysis of CN-AML bone marrow (n = 7) confirmed that NME1 mRNA is always decreased during storage, while NME2 mRNA is either decreased or maintained. We conclude that ex vivo stress can reveal novel prognostic markers.
authors.affiliation: Department of Hematology, Oncology and Hemostasiology, University of Leipzig, Leipzig, Germany.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bach
authors.forename: Rainer
authors.initials: R
authors.lastname: Krahl
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Frank
authors.initials: F
authors.lastname: Schüler
authors.forename: Haifa
authors.initials: H
authors.lastname: Al-Ali
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Gottfried
authors.initials: G
authors.lastname: Dölken
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Michael
authors.initials: M
authors.lastname: Cross
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism*; D015331:Cohort Studies; D003582:Cytogenetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C517938:NME1 protein, human; C517940:NME2 protein, human