ORIGINAL ARTICLE

Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia

P Vorwerk¹, H Wex¹, B Hohmann¹, K Mohnike², U Schmidt³ and U Mittler¹

¹ Department of Paediatric Oncology, Otto-von-Guericke-University Magdeburg, Emanuel-Larisch-Weg 17–19, D-39112 Magdeburg, Germany
² Department of Paediatric Endocrinology, Otto-von-Guericke-University Magdeburg
³ Institute of Biometrics and Medical Informatics, Otto-von-Guericke-University Magdeburg

Correspondence to:
Correspondence to:
Dr P Vorwerk, Otto-von-Guericke-University, Department of Paediatric Oncology, Emanuel-Larisch-Weg 17–19, D-39112 Magdeburg, Germany;
Peter.Vorwerk{at}medizin.uni-magdeburg.de

Background: Alterations in the insulin-like growth factor (IGF) system have been reported for different tumours. They are of particular interest in the search for new prognostic and therapeutic approaches in cancer. In childhood acute lymphoblastic leukaemia (ALL) the amount of "tumour mass" at diagnosis can exceed 1 kg. To understand the endocrine, paracrine, and autocrine potential of the malignant transformed progenitor cells, the ability of these cells to express components of the IGF system needs to be investigated.

Aim: To characterise the expression pattern of genes of the IGF system in malignant lymphoblasts of children suffering from ALL.

Methods: Reverse transcription polymerase chain reaction of Ficoll separated mononuclear cells from 142 children with ALL, 127 cord blood samples, and 55 blood samples of age matched controls were studied.

Results: The expression of IGF-I, IGF-II, IGF binding protein 5 (IGFBP-5), and CTGF (IGFBP-rP2) was seen in a higher proportion of mononuclear cells of patients with ALL than in controls. Patients with ALL who were in continuous remission had a lower percentage of IGFBP-2 and IGFBP-3 expressing mononuclear cells at diagnosis than did those who developed a relapse. Only malignant lymphoblasts of B cell origin showed expression of CTGF (IGFBP-rP2). Malignant lymphoblasts of T cell origin more often expressed IGFBP-2 and IGFBP-5, whereas IGF-II and IGFBP-3 expression was seen more often in lymphoblasts of B cell origin.

Conclusions: Malignant lymphoblasts of patients with ALL express components of the IGF system and therefore promote their own growth in an autocrine, paracrine, or endocrine manner. Whether these components will be useful as prognostic factors in the stratification of ALL treatment in children needs to be evaluated.

Abbreviations: ALL, acute lymphoblastic leukaemia; ALS, acid labile subunit; B-ALL, B cell ALL; BFM, Berlin-Frankfurt-Münster; IGF, insulin-like growth factor; IGFBP, IGF binding protein; IGFBP-rP, IGFBP related protein; RT-PCR, reverse transcription polymerase chain reaction; T-ALL, T cell ALL

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