BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia

• Verfasst von: Heesch, Sandra Anja [VerfasserIn]
• Verfasst von: Schlee, C. [VerfasserIn]
• Verfasst von: Neumann, M. [VerfasserIn]
• Verfasst von: Stroux, A. [VerfasserIn]
• Verfasst von: Kühnl, A. [VerfasserIn]
• Verfasst von: Schwartz, S. [VerfasserIn]
• Verfasst von: Haferlach, T. [VerfasserIn]
• Verfasst von: Goekbuget, N. [VerfasserIn]
• Verfasst von: Hoelzer, D. [VerfasserIn]
• Verfasst von: Thiel, E. [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Baldus, C. D. [VerfasserIn]
• Titel: BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia
• Verf.angabe: S. Heesch, C. Schlee, M. Neumann, A. Stroux, A. Kühnl, S. Schwartz, T. Haferlach, N. Goekbuget, D. Hoelzer, E. Thiel, W.-K. Hofmann, C. D. Baldus
• E-Jahr: 2010
• Jahr: 10 June 2010
• Umfang: 8 S.
• Fussnoten: Gesehen am 11.04.2023
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2010
• Band/Heft Quelle: 24(2010), 8, Seite 1429-1436
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2010.130
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Acute lymphocytic leukaemia
• Sach-SW: Acute myeloid leukaemia
• Sach-SW: Cancer therapeutic resistance
• Sach-SW: Gene expression profiling
• K10plus-PPN: 184195554X

Abstract

Over expression of BAALC (brain and acute leukemia, cytoplasmic) predicts an inferior outcome in acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. To identify BAALC-associated genes that give insights into its functional role in chemotherapy resistance, gene expression signatures differentiating high from low BAALC expressers were generated from normal CD34+ progenitors, T-acute lymphoblastic leukemia (T-ALL) and AML samples. The insulin-like growth factor binding protein 7 (IGFBP7) was one of the four genes (CD34, CD133, natriuretic peptide receptor C (NPR3), IGFBP7) coexpressed with BAALC and common to the three entities. In T-ALL, high IGFBP7-expression was associated with an immature phenotype of early T-ALL (P<0.001), expression of CD34 (P<0.001) and CD33 (P<0.001). Moreover, high IGFBP7-expression predicted primary therapy resistance (P=0.03) and inferior survival in T-ALL (P=0.03). In vitro studies revealed that IGFBP7 protein significantly inhibited the proliferation of leukemia cell lines (Jurkat cells: 42% reduction, P=0.002; KG1a cells: 65% reduction, P<0.001). In conclusion, IGFBP7 was identified as a BAALC coexpressed gene. Furthermore, high IGFBP7 was associated with stem cell features and treatment failure in T-ALL. In contrast to BAALC, which likely represents only a surrogate marker of treatment failure in acute leukemia, IGFBP7 regulates the proliferation of leukemic cells and might be involved in chemotherapy resistance.