Connective tissue growth factor (CTGF) expression and outcome in adult patients with acute lymphoblastic leukemia

Abstract

We compared the gene expression profile of adult acute lymphoblastic leukemia (ALL) to normal hematopoietic and non-ALL samples using oligonucleotide arrays. Connective tissue growth factor (CTGF) was the highest overexpressed gene in B-cell ALL compared with the other groups, and displayed heterogeneous expression, suggesting it might have prognostic relevance. CTGF expression was examined by quantitative reverse transcriptase-polymerase chain reaction (ORT-PCR) on 79 adult ALL specimens. CTGF expression levels were significantly increased in ALL cases with B-lineage (P < .001), unfavorable cytogenetics (P < .001), and blasts expressing CD34 (P < .001). In a multivariate proportional hazards model, higher CTGF expression levels corresponded to worsening of overall survival (OS; hazard ratio 1.36, for each 10-fold increase in expression; P = .019). Further studies are ongoing to confirm the prognostic value of CTGF expression in ALL and to investigate its role in normal and abnormal lymphocyte biology.

Figures

Figure 1

CTGF expression levels in acute leukemias and normal controls, and overall survival of a series of adult acute lymphoblastic leukemia patients by CTGF expression levels. (A) CTGF expression level in different specimens in HG U133A arrays. The intensity of expression is in log2 scale. AML indicates acute myeloid leukemia; B-ALL, B-cell acute lymphoblastic leukemia; T-ALL, T-cell acute lymphoblastic leukemia; U-ALL, acute lymphoblastic leukemia of unknown lineage; PBSCD34, CD34-enriched cells derived from G-CSF–mobilized peripheral blood; NBM, normal bone marrow; CD22, CD22+-selected B cells from normal peripheral blood (2 samples in duplicate); NPB, normal peripheral blood; BMCD34, CD34-enriched cells from normal bone marrow. (B) Overall survival in ALL patients in high, intermediate, and low CTGF expression tertiles, measured by Q-RT-PCR.