Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease

L. Teofili, A. L. Di Febo, F. Pierconti, N. Maggiano, M. Bendandi, S. Rutella, A. Cingolani, N. Di Renzo, P. Musto, S. Pileri, G. Leone, L. M. Larocca

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Abstract

The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus-positive (EBV+) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF+. These results were independent of the EBV infection. Interestingly, several HGF+ dendritic-reticulum cells were found scattered around c-MET+ RS cells. The mean ± SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 ± 91 (95% confidence interval [CL], 1221-1585) and 1497 ± 242 pg/mL (95% Cl, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 ± 28 pg/mL; 95% Cl, 600-721; and P <.001 for both groups of patients) and of HD patients in remission (616 ± 49 pg/mL; 95% Cl, 517-714; and P <.001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (p= .014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of Rs cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.

Original languageEnglish
Pages (from-to)1063-1069
Number of pages7
JournalBlood
Volume97
Issue number4
DOIs
Publication statusPublished - Feb 15 2001

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Hepatocyte Growth Factor
Proto-Oncogenes
Hodgkin Disease
Reed-Sternberg Cells
Ligands
Biopsy
Serum
Human Herpesvirus 4
Bone
Lymph Nodes
Bone Marrow
Proto-Oncogene Proteins c-met
Reticulum
Epstein-Barr Virus Infections
Viruses
Protein-Tyrosine Kinases
Dendritic Cells
Cell Survival
Adhesion
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Teofili, L., Di Febo, A. L., Pierconti, F., Maggiano, N., Bendandi, M., Rutella, S., ... Larocca, L. M. (2001). Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. Blood, 97(4), 1063-1069. https://doi.org/10.1182/blood.V97.4.1063

Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. / Teofili, L.; Di Febo, A. L.; Pierconti, F.; Maggiano, N.; Bendandi, M.; Rutella, S.; Cingolani, A.; Di Renzo, N.; Musto, P.; Pileri, S.; Leone, G.; Larocca, L. M.

In: Blood, Vol. 97, No. 4, 15.02.2001, p. 1063-1069.

Research output: Contribution to journalArticle

Teofili, L, Di Febo, AL, Pierconti, F, Maggiano, N, Bendandi, M, Rutella, S, Cingolani, A, Di Renzo, N, Musto, P, Pileri, S, Leone, G & Larocca, LM 2001, 'Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease', Blood, vol. 97, no. 4, pp. 1063-1069. https://doi.org/10.1182/blood.V97.4.1063
Teofili L, Di Febo AL, Pierconti F, Maggiano N, Bendandi M, Rutella S et al. Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. Blood. 2001 Feb 15;97(4):1063-1069. https://doi.org/10.1182/blood.V97.4.1063
Teofili, L. ; Di Febo, A. L. ; Pierconti, F. ; Maggiano, N. ; Bendandi, M. ; Rutella, S. ; Cingolani, A. ; Di Renzo, N. ; Musto, P. ; Pileri, S. ; Leone, G. ; Larocca, L. M. / Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. In: Blood. 2001 ; Vol. 97, No. 4. pp. 1063-1069.
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abstract = "The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus-positive (EBV+) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF+. These results were independent of the EBV infection. Interestingly, several HGF+ dendritic-reticulum cells were found scattered around c-MET+ RS cells. The mean ± SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 ± 91 (95{\%} confidence interval [CL], 1221-1585) and 1497 ± 242 pg/mL (95{\%} Cl, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 ± 28 pg/mL; 95{\%} Cl, 600-721; and P <.001 for both groups of patients) and of HD patients in remission (616 ± 49 pg/mL; 95{\%} Cl, 517-714; and P <.001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (p= .014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of Rs cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.",
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AU - Bendandi, M.

AU - Rutella, S.

AU - Cingolani, A.

AU - Di Renzo, N.

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AU - Leone, G.

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