Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations
A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2012
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| In: |
Blood cancer journal
Year: 2012, Jahrgang: 2, Heft: 1 |
| ISSN: | 2044-5385 |
| DOI: | 10.1038/bcj.2011.49 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/bcj.2011.49 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/bcj201149 
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| Verfasserangaben: | M. Neumann, S. Heesch, N. Gökbuget, S. Schwartz, C. Schlee, O. Benlasfer, N. Farhadi-Sartangi, J. Thibaut, T. Burmeister, D. Hoelzer, W.-K. Hofmann, E. Thiel, C. D. Baldus |
| Zusammenfassung: | A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93-07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL. |
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| Beschreibung: | Published online 27 January 2012 Gesehen am 28.06.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 2044-5385 |
| DOI: | 10.1038/bcj.2011.49 |