High expression of connective tissue growth factor in pre‐B acute lymphoblastic leukaemia

• Published in: British journal of haematology Vol. 138; no. 6; pp. 740 - 748
• Main Authors: Boag, Joanne M., Beesley, Alex H., Firth, Martin J., Freitas, Joseph R., Ford, Jette, Brigstock, David R., De Klerk, Nicholas H., Kees, Ursula R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2007; Blackwell
• Subjects: acute lymphoblastic leukaemia; Biological and medical sciences; Blotting, Western; Case-Control Studies; Child; Connective Tissue Growth Factor; Culture Media, Conditioned - chemistry; Fetal Blood - chemistry; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Immediate-Early Proteins - analysis; Immediate-Early Proteins - genetics; Intercellular Signaling Peptides and Proteins - analysis; Intercellular Signaling Peptides and Proteins - genetics; leukaemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; microarray; Oligonucleotide Array Sequence Analysis; paediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Human; Hematology; Precursor cell; Acute leukemia; Connective tissue growth factor; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Lymphoid neoplasm; paediatrics; microarray; Lymphoproliferative syndrome; acute lymphoblastic leukaemia; leukaemia; Acute lymphocytic leukemia; Child
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2007.06739.x

Summary In recent years microarrays have been used extensively to characterize gene expression in acute lymphoblastic leukaemia (ALL). Few studies, however, have analysed normal haematopoietic cell populations to identify altered gene expression in ALL. We used oligonucleotide microarrays to compare the gene expression profile of paediatric precursor‐B (pre‐B) ALL specimens with two control cell populations, normal CD34+ and CD19+IgM− cells, to focus on genes linked to leukemogenesis. A set of eight genes was identified with a ninefold higher average expression in ALL specimens compared with control cells. All of these genes were significantly deregulated in an independent cohort of 101 ALL specimens. One gene, connective tissue growth factor (CTGF, also known as CCN2), had exceptionally high expression, which was confirmed in three independent leukaemia studies. Further analysis of CTGF expression in ALL revealed exclusive expression in B‐lineage, not T‐lineage, ALL. Within B‐lineage ALL approximately 75% of specimens were consistently positive for CTGF expression, however, specimens containing the E2A‐PBX1 translocation showed low or no expression. Protein studies using Western blot analysis demonstrated the presence of CTGF in ALL cell‐conditioned media. These findings indicate that CTGF is secreted by pre‐B ALL cells and may play a role in the pathophysiology of this disease.