Platelet-derived growth factor (PDGF) regulates clonal proliferation of malignant pre-B cell lines, but little is known about its role in normal B lymphocyte differentiation and malignant transformation. To understand the expression of PDGF-A, PDGF-B and the β-receptor (PDGF-Rβ) in B cell lymphoproliferative disorders, we used an immunohistochemical method to stain formalin-fixed, paraffin-embedded tissues in 5 patients with reactive lymphoid hyperplasia, 15 with non-Hodgkin’s lymphoma and 23 with B cell chronic lymphocytic leukemia (B-CLL). Abundant PDGF-A, rather than PDGF-B, was expressed in normal B cell differentiation. There was no difference in the expression of PDGF-A and PDGF-B between patients with reactive lymphoid hyperplasia and patients with malignant lymphoproliferative disorders. Among the patients with B-CLL, the expression of PDGF-B was much stronger than the expression of PDGF-A, and 18 of the patients had coexpression of PDGF-B and PDGF-Rβ. A larger proportion of patients with B-CLL than with non-Hodgkin’s lymphoma had expression of PDGF-B and PDGF-Rβ. In conclusion, PDGF-A expression in all stages of B lymphocyte differentiation suggests that it is important in B cell differentiation and proliferation. Expression of PDGF-B and PDGF-Rβ suggests that autocrine signaling of PDGF may be important in malignant transformation of B-CLL. However, further studies are necessary to confirm these conclusions.

Keywords:
Chronic lymphocytic leukemia, Immunohistochemistry, Non-Hodgkin’s lymphoma, Platelet-derived growth factor
1.
Harrison P, Cramer EM: Platelet alpha-granules. Blood Rev 1993;7:52–62.
2.
Heldin CH, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79:1283–1316.
3.
Li X, Ponten A, Aase K, Karlsson L, Abramsson A, Uutela M, Backstrom G, Hellstrom M, Bostrom H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U: PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol 2000;2:302–309.
4.
Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U: PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol 2001;3:512–516.
5.
Ostman A, Heldin CH: Involvement of platelet-derived growth factor in disease: Development of specific antagonists. Adv Cancer Res 2001;80:1–38.
6.
Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB: Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000;295:139–145.
7.
Schiffer CA: Signal transduction inhibition: Changing paradigms in cancer care. Semin Oncol 2001;28(suppl 17):34–39.
8.
Michalevicz R, Katz F, Stroobant P, Janossy G, Tindle RW, Hoffbrand AV: Platelet-derived growth factor stimulates growth of highly enriched multipotent haemopoietic progenitors. Br J Haematol 1986;63:591–598.
9.
Michalevicz R, Francis GE, Price GM, Hoffbrand AV: The role of platelet-derived growth factor on human pluripotent progenitor (CFU-GEMM) growth in vitro. Leuk Res 1985;9:399–405.
10.
Nara N, Tohda S, Nagata K, Suzuki T, Yamashita Y, Imai Y: Effect of platelet-derived growth factor on the proliferation of blast progenitors from acute myeloblastic leukemia patients. Acta Haematol 1990;83:187–192.
11.
Katz FE, Michalevicz R, Lam G, Hoffbrand AV, Goldman JM: Effect of platelet-derived growth factor on enriched populations of haemopoietic progenitors from patients with chronic myeloid leukaemia. Leuk Res 1987;11:339–344.
12.
Caenazzo A, Pietrogrande F, Polato G, Piva E, Masiero M, Sgarabotto D, Girolami A: Changes in the mitogenic activity of platelet-derived growth factor(s) in patients with myeloproliferative disease. Acta Haematol 1989;81:131–135.
13.
Tsai LH, White L, Raines E, Ross R, Smith RG, Cushley W, Ozanne B: Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines. Blood 1994;83:51–55.
14.
Trink B, Wang G, Shahar M, Meydan N, Roifman CM: Functional platelet-derived growth factor-beta (PDGF-beta) receptor expressed on early B-lineage precursor cells. Clin Exp Immunol 1995;102:417–424.
15.
Yoon SY, Tefferi A, Li CY: Cellular distribution of platelet-derived growth factor, transforming growth factor-beta, basic fibroblast growth factor, and their receptors in normal bone marrow. Acta Haematol 2000;104:151–157.
16.
Beckmann MP, Betsholtz C, Heldin CH, Westermark B, Di Marco E, Di Fiore PP, Robbins KC, Aaronson SA: Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science 1988;241:1346–1349.
17.
Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN: Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 1983;221:275–277.
18.
Meyer-Ingold W, Eichner W: Platelet-derived growth factor. Cell Biol Int 1995;19:389–398.
19.
Williams LT: Signal transduction by the platelet-derived growth factor receptor. Science 1989;243:1564–1570.
20.
Foss B, Ulvestad E, Bruserud O: Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts. Eur J Haematol 2001;66:365–376. Corrected and republished in: Eur J Haematol 2001;67:267–278.
21.
Molica S, Vitelli G, Levato D, Ricciotti A, Digiesi G: Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia. Br J Cancer 2002;86:31–35.
22.
Salven P, Orpana A, Teerenhovi L, Joensuu H: Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: A single-institution study of 200 patients. Blood 2000;96:3712–3718.
23.
Menzel T, Rahman Z, Calleja E, White K, Wilson EL, Wieder R, Gabrilove J: Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood 1996:87:1056–1063.
24.
Konig 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.
25.
Bairey O, Zimra Y, Shaklai M, Rabizadeh E: Bcl-2 expression correlates positively with serum basic fibroblast growth factor (bFGF) and negatively with cellular vascular endothelial growth factor (VEGF) in patients with chronic lymphocytic leukaemia. Br J Haematol 2001;113:400–406.
26.
Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ: Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 1996;87:619–628.
27.
Mavromatis B, Cheson BD: Monoclonal antibody therapy of chronic lymphocytic leukemia. J Clin Oncol 2003;21:1874–1881.
© 2005 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.