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

Leukemia. 2010 Aug;24(8):1429-36. doi: 10.1038/leu.2010.130. Epub 2010 Jun 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Base Sequence
  • Biomarkers, Tumor*
  • Cell Line, Tumor
  • DNA Primers
  • DNA Replication
  • Gene Expression Profiling*
  • Humans
  • Immunophenotyping
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Leukemia, B-Cell / genetics*
  • Leukemia, Myeloid, Acute / genetics*
  • Neoplasm Proteins / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*


  • BAALC protein, human
  • Biomarkers, Tumor
  • DNA Primers
  • Insulin-Like Growth Factor Binding Proteins
  • Neoplasm Proteins
  • insulin-like growth factor binding protein-related protein 1