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Substance P – a potent risk factor in childhood lymphoblastic leukaemia

Abstract

The study focused on determining the expression of substance P (SP) in neoplastic bone marrow cells in childhood acute lymphoblastic leukaemia (ALL) in terms of its mRNA and the level of protein production. An attempt has also been made to demonstrate a correlation of SP with leukaemia risk factors and treatment failure. The study group comprised 120 children treated for ALL. Expression of SP was examined by in situ hybridisation with a 5′-biotinylated probe and by immunocytochemistry with specific anti-human SP antibody. Out of 80 patients with common ALL, the expression of SP was demonstrated in 33 cases (41.2%). In the group of 24 children with pre-B ALL, the presence of SP was noted in six cases (25.0%). Of 16 patients with T-cell leukaemia, SP expression was demonstrated in 13 cases (81.2%). The percentage of immunopositive cells in the SP-positive cases ranged from 79.8 to 97.3. Treatment failure in the children with ALL was closely related to the expression of SP observed at the beginning of treatment. The results showed a connection between the presence of SP-positive blasts and leukaemia relapse. This may indicate that SP expression, involved in the proliferation of the tumour cells, may represent a novel risk factor in ALL.

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References

  1. Maggio J . Tachykinins. Ann Rev Neurosci 1990; 11: 13–26.

    Article  Google Scholar 

  2. Rameshwar P, Gascon P . Haematopoietic modulation by the tachykinins. Acta Hematol 1997; 98: 59–64.

    Article  CAS  Google Scholar 

  3. Rameshwar P, Gascon P . Substance P (SP) mediates production of stem cell factor and interleukin-1 in bone marrow stroma: potential autoregulatory role for these cytokines in SP receptor expression and induction. Blood 1995; 86: 482–490.

    CAS  PubMed  Google Scholar 

  4. Felten D, Felten S, Carlson S . Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 1985; 135(Suppl. 2): 7559–7655.

    Google Scholar 

  5. Savino W, Dardenne M . Immuno-neuroendocrine interactions. Immunol Today 1995; 16: 318–329.

    Article  CAS  Google Scholar 

  6. Sirinek L, O'Dorisio M . Modulation of immune function by intestinal neuropeptides. Acta Oncologica 1991; 30: 509–518.

    Article  CAS  Google Scholar 

  7. Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather A, D'Angio G . Report and recommendations of the Rome Workshop concerning poor-prognosis acute lymphoblastic leukaemia in children: biologic bases for staging, stratifications and treatment. Med Pediatr Oncol 1986; 14: 191–194.

    Article  CAS  Google Scholar 

  8. Raimondi SC . Current status of cytogenetic research in childhood acute lymphoblastic leukalemia. Blood 1993; 81: 2237–2251.

    CAS  Google Scholar 

  9. Schultz KR, Massing B, Spinelli JJ . Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome in children with acute lymphoblastic leukaemia. Med Pediatr Oncol 1997; 29: 16–22.

    Article  CAS  Google Scholar 

  10. Volm M, Zintl F, Edler L, Sauerbrey A . Prognostic value of protein kinase C, proto-oncogene products and resistance-related proteins in newly diagnosed childhood lymphoblastic leukaemia. Med Pediatr Oncol 1997; 28: 117–126.

    Article  CAS  Google Scholar 

  11. Steinherz PG, Gaynon PS, Miller DR, Reaman G, Bleyer A, Finklestein J et al. Improved disease-free survival of children with acute lymphoblastic leukaemia at high risk for early relapse with New York regimen – a new intensive therapy protocol: a report from Children's Cancer Study Group. J Clin Oncol 1986; 4: 744–752.

    Article  CAS  Google Scholar 

  12. Reihm H . Multizentrische Therapiestudie ALL-BFM-90 zur Behandlung von Kindern und Jugendlichen mit Akuter Lymphoblastischer Leukämie (Non-B-ALL). Hannover: Therapieprotokoll, 1991.

    Google Scholar 

  13. Nowicki M, Miskowiak B, Kaczmarek-Kanold M, Partyka M . Prognoza ewolucji hipoplazji szpiku kostnego w oparciu o immunocytochemiczne wystpowanie substancji P. Prz Ped 2001; 31: 273–277.

    Google Scholar 

  14. Hsu S, Raine L, Fanger H . Use of avidin–biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981; 29: 577–580.

    Article  CAS  Google Scholar 

  15. Shi SR, Cote RJ, Taylor CR . Antigen retrieval immunocytochemistry: past, present and future. J Histochem Cytochem 1997; 45: 327–343.

    Article  CAS  Google Scholar 

  16. Crist WM, Grosse CE, Pullen J . Immunologic markers in childhood acute lymphoblastic leukaemia. Semin Oncol 1985; 12: 105–112.

    CAS  PubMed  Google Scholar 

  17. Coghlan J, Aldred P, Haralambidis J, Niall H, Penschow J, Tregear G . Hybridisation histochemistry. Anal Biochem, 1985; 149: 1–28.

    Article  CAS  Google Scholar 

  18. Elias J, Gown A, Nakamura R . Special report: quality control in immunohistochemistry. Am J Clin Pathol 1989; 92: 836–843.

    Article  CAS  Google Scholar 

  19. Nowicki M, Miskowiak B, Konwerska A . Expression of CD79a antigen in acute lymphoblastic leukaemia in children. Folia Histochem Cytobiol 1999; 37: 149–150.

    CAS  PubMed  Google Scholar 

  20. Rameshwar P, Ganea D, Gascon P . In vitro effect of substance P on hematopoiesis. Blood 1993; 81: 391–399.

    CAS  Google Scholar 

  21. Lambrecht B, Germonpre P, Evereart E, Carro-Muino I, DeVeerman M, de Filipe C et al. Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct Tcr ligation. Eur J Immunol 1999; 29: 3815–3825.

    Article  CAS  Google Scholar 

  22. Rameshwar P, Poddar A, Gascon P . Haematopoietic regulation mediated by interactions among the neurokinins and cytokines. Leukemia Lymphoma 1997; 28: 1–10.

    Article  CAS  Google Scholar 

  23. Watt S, Chan J . CD164 – a novel sialomucin on CD 34+ cells. Leukemia Lymphoma 2000; 37: 1–25.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Professor Geoffrey Shaw for his assistance with the English text.

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Nowicki, M., Miśkowiak, B. Substance P – a potent risk factor in childhood lymphoblastic leukaemia. Leukemia 17, 1096–1099 (2003). https://doi.org/10.1038/sj.leu.2402920

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