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Verfasst von:Neumann, Martin [VerfasserIn]   i
 Hofmann, Wolf-Karsten [VerfasserIn]   i
Titel:FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors
Verf.angabe:Martin Neumann, Ebru Coskun, Lars Fransecky, Liliana H. Mochmann, Isabelle Bartram, Nasrin Farhadi Sartangi, Sandra Heesch, Nicola Gökbuget, Stefan Schwartz, Christian Brandts, Cornelia Schlee, Rainer Haas, Ulrich Dührsen, Martin Griesshammer, Hartmut Döhner, Gerhard Ehninger, Thomas Burmeister, Olga Blau, Eckhard Thiel, Dieter Hoelzer, Wolf-Karsten Hofmann, Claudia D. Baldus
Jahr:2013
Fussnoten:Published: January 24, 2013 ; Gesehen am 26.06.2018
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2013
Band/Heft Quelle:8(2013,1) Artikel-Nummer e53190, 10 Seiten
ISSN Quelle:1932-6203
Abstract:Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.
DOI:doi:10.1371/journal.pone.0053190
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: http://dx.doi.org/10.1371/journal.pone.0053190
 kostenfrei: Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053190
 DOI: https://doi.org/10.1371/journal.pone.0053190
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Acute myeloid leukemia
 Apoptosis
 Chemotherapy
 Gene expression
 Leukemias
 Pediatrics
 T cells
 Tyrosine kinase inhibitors
K10plus-PPN:1576867919
Verknüpfungen:→ Zeitschrift

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