Bystander Cells and Prognosis in Hodgkin Lymphoma

Hodgkin lymphoma (HL) is characterised histologically by a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells surrounded by benign cells, and clinically by a relatively good prognosis. The treatment, however, leads to a risk of serious side effects. Knowledge about the biology of the disease, particularly the interaction between the HRS cells and the surrounding cells, is essential in order to improve diagnosis and treatment. HL patients with abundant eosinophils in the tumours have a poor prognosis, therefore the eosinophil derived protein eosinophil cationic protein (ECP) was studied. Serum-ECP (S-ECP) was elevated in most HL patients. It correlated to number of tumour eosinophils, nodular sclerosis (NS) histology, and the negative prognostic factors high erythrocyte sedimentation rate (ESR) and blood leukocyte count (WBC). A polymorphism in the ECP gene (434(G>C)) was identified and the 434GG genotype correlated to NS histology and high ESR…

Contents

INTRODUCTION
Thomas Hodgkin and the early reports of the disease
Why the disease changes name in the thesis
Dorothy Reed and Carl Sternberg describing the malignant Cell
The never-ending story of lymphoma classifications
The tumour cell
The bystander cells
Eosinophilic granulocytes
Eosinophil cationic protein (ECP)
Mast cells
Polymorphisms
Epidemiology and aetiology of HL
Clinical investigations and staging
Prognostic factors
Factors related to the HRS cells, tumour burden, and dissemination of the disease
Factors related to the cellular composition of the tumours
Factors related to inflammatory activity and the release of cytokines and other factors
Host related prognostic factors
Prognostic scores
Treatment and prognosis
Treatment and problems in patients with early and intermediate stage HL
AIM OF THE STUDY
MATERIAL & METHODS
Patients and clinical characteristics
Treatment and staging according to the National Care
Programme
Serum proteins
Immunohistochemistry
Cell cultures
Reverse transcription polymerase chain reaction (RT-PCR)
Flow cytometry
Endonuclease restriction digestion
Calculation of isoelectric point (pI)
Statistical analysis
RESULTS
Eosinophils in HL (I, II)
Tissue eosinophilia and serum ECP (I)
ECP polymorphisms (II)
Mast cells in HL (III, IV)
Expression of CD30L on mast cells and stimulation of HRS (III)
Mast cell infiltration and prognosis (IV)
HL in early and intermediate stages – treatment and prognosis (V)
DISCUSSION
Bystander cells in HL
Eosinophils in HL
Tissue eosinophilia
ECP
ECP polymorphisms
Mast cells in HL
Expression of CD30L and stimulation of HRS
Mast cells and prognosis
Early and intermediate stages
Treatment and prognosis
Prognostic factors
CONCLUSIONS
FUTURE PROSPECTS
Preclinical research
Treatment
Prognostic factors
ACKNOWLEDGEMENTS
REFERENCES

Author: Molin, Daniel

Source: Uppsala University Library

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