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The growth of highly proliferative acute lymphoblastic leukemia may be independent of stroma and/or angiogenesis

Leukemia volume 15, pages 1143–1145 (2001)Cite this article

Lymphoproliferative diseases, like acute leukemia (AL) in children, have potential to invade locally and infiltrate a variety of different tissues other than bone marrow, ie central nervous system or testis. The mechanisms of tumoral invasion involved in solid tumors are related to angiogenesis, endothelial adhesion and cell migration. Recent studies have hypothesized similar mechanisms for hemopathies, especially AL.1 It has been suggested that angiogenesis could participate in AL cell proliferation, and therefore the secretion of modulators of angiogenesis such as bFGF has been considered as a possible indicator of the leukemic proliferation. The importance of angiogenic factors is not fully established. These angiogenic cytokines seem to be produced by leukemic and/or bone marrow (BM) microenvironmental cells.2 Recently, Veiga et al2 have shown a contact-dependent interaction between acute lymphoblastic leukaemia (ALL) cells of patients and BM endothelium in presence of angiogenic cytokines. This interaction leads to the survival of leukemic cells by maintaining the expression of anti-apoptotic genes. A recent study showed that high levels of cellular VEGF are significantly correlated with shorter survival in adult acute myeloblastic leukemia (AML) patients with high WBC at diagnosis (P < 0.04), whereas no association was found with the plasma levels of bFGF.3 However, no correlation between angiogenesis and the prognosis of ALL has been described yet.

In a series of children with ALL, we found a correlation between usual poor prognostic features and the interactions between leukemic cells and BM microenvironment. Twenty-three newly diagnosed pro-B and pre-B-lineage ALL were studied for the urinary secretion of angiogenic cytokines (bFGF, VEGF). Diagnosis was established on BM aspirates and classification was made according to the usual immunophenotyping and cytogenetics. All children were treated according to the French protocol FRALLE 93.4 The urinary bFGF and VEGF levels (pg/mmol creatinine/24 h) were determined by an ELISA method using the Quantikine FGF immunoassay (R&D Systems, Minneapolis, MN, USA) performed on a 24-h urine collection.

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References

  1. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J . Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia Am J Pathol 1997 150: 815–821

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Veiga JP, Sallan SE, Nadler LM, Cardoso AA . De novo angiogenesis confers a selective advantage to leukemic cells through contact-dependent maintenance of anti-apoptotic gene expression Blood 1999 94 (Suppl. 1): 658a

    Google Scholar 

  3. Aguayo A, Estey E, Kantarjian H, Mansouri T, Gidel C, Keating M, Giles F, Estrov Z, Barlogie B, Albitar M . Cellular VEGF is a predictor of outcome in patients with acute myeloblastic leukemia Blood 1999 94: 3717–3721

    CAS  PubMed  Google Scholar 

  4. Schaison G, Baruchel A, Leblanc T, Auclerc MF . Therapy of childhood acute lymphoblastic leukemia Int J Ped Hematol/Oncol 1998 5: 145–154

    Google Scholar 

  5. Hussong JW, Rodgers GM, Shami PJ . Evidence of increased angiogenesis in patients with acute myeloid leukemia Blood 2000 95: 309–313

    CAS  PubMed  Google Scholar 

  6. Brunner G, Nguyen H, Gabrilove J, Rifkin DB, Wilson EL . Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells Blood 1993 81: 631–638

    CAS  Google Scholar 

  7. König A, Menzel T, Lynen S, Wrazel L, Rosen A, Al-Katib A, Raveche E, Gabrilove JL . Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis Leukemia 1997 11: 258–265

    Article  Google Scholar 

  8. Okunieff P, Barrett AJ, Phang SE, Li A, Constine LS, Williams JP, Rubin P, Wang X, Wu T, Chen Y, Ding I . Circulating basic fibroblastic growth factor declines during Cy/TBI Bone Marrow Transplant 1999 23: 1117–1121

    Article  CAS  Google Scholar 

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  1. Groupe de Recherche sur le Microenvironnement et le Renouvellement Cellulaire Intégré, Rouen, France

    P Schneider & J-P Vannier

  2. Hôpital Charles-Nicolle, Hemato-Oncologie Pédiatrique, Rouen, France

    P Schneider, M Vasse, E Sbaa-Ketata, L Hong, C Soria & J-P Vannier

  3. Hôpital Charles-Nicolle, Laboratoire Hématologie, Rouen, France

    M Vasse & B Lenormand

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  1. P Schneider
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Schneider, P., Vasse, M., Sbaa-Ketata, E. et al. The growth of highly proliferative acute lymphoblastic leukemia may be independent of stroma and/or angiogenesis. Leukemia 15, 1143–1145 (2001). https://doi.org/10.1038/sj.leu.2402141

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