Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

M.D. Welch; M. Howlett; H.M. Halse; W.K. Greene; U.R. Kees

doi:10.1016/j.leukres.2015.05.008

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Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

Journal article

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Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

M.D. Welch, M. Howlett, H.M. Halse, W.K. Greene and U.R. Kees

Leukemia Research, Vol.39(8), pp.913-920

2015

DOI: https://doi.org/10.1016/j.leukres.2015.05.008

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Abstract

Introduction: Connective tissue growth factor (CTGF/. CCN2) has been shown previously to be aberrantly expressed in a high proportion of paediatric precursor B cell acute lymphoblastic leukaemia (pre-B ALL), suggesting a potential oncogenic role in this tumour type. We therefore assessed CTGF mRNA transcript diversity in B-lineage ALL using primary patient specimens and cell lines. Methods: CTGF mRNA expression was evaluated by quantitative real-time PCR and Northern blotting. We performed a structural analysis of CTGF mRNA by nested reverse-transcriptase PCR and examined CTGF protein diversity by immunoblotting. Results: Northern blot analysis of pre-B ALL cell lines revealed short CTGF transcripts that were expressed in association with the active phase of cellular growth. Structural analysis confirmed the synthesis of several novel CTGF mRNA isoforms in B-lineage ALL cell lines that were uniformly characterised by the retention of the coding sequence for the C-terminal (CT) domain. One of these novel spliceforms was expressed in a majority (70%) of primary pre-B ALL patient specimens positive for canonical CTGF mRNA. Evidence that these alternative transcripts have coding potential was provided by cryptic CTGF proteins of predicted size detected by immunoblotting. Conclusion: This study identifies for the first time alternative splicing of the CTGF gene and shows that a short CTGF splice variant associated with cell proliferation is expressed in most cases of primary CTGF-positive pre-B ALL. This novel variant encoding only the CT domain may play a role in pre-B ALL tumorigenesis and/or progression.

Details

Title: Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia
Authors/Creators: M.D. Welch (Author/Creator) - The Kids Research Institute Australia
M. Howlett (Author/Creator) - The Kids Research Institute Australia
H.M. Halse (Author/Creator) - The Kids Research Institute Australia
W.K. Greene (Author/Creator) - Murdoch University
U.R. Kees (Author/Creator) - The Kids Research Institute Australia
Publication Details: Leukemia Research, Vol.39(8), pp.913-920
Publisher: Elsevier BV
Identifiers: 991005543999307891
Copyright: © 2015 Elsevier Ltd.
Murdoch Affiliation: School of Veterinary and Life Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.132 Extracellular Matrix & Cell Differentiation; 1.132.306 TGF-Beta
Web Of Science research areas: Hematology; Oncology
ESI research areas: Clinical Medicine