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DISTRIBUTION OF T‐CELL SIGNALLING MOLECULES IN HUMAN MYELOMA
Author(s) -
Bianchi Alberto,
Mariani Sara,
Beggiato Eloise,
Borrione Paolo,
Peola Silvia,
Boccadoro Mario,
Pileri Alessandro,
Massaia Massimo
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.1482961.x
Subject(s) - fyn , protein kinase c , cd3 , t cell receptor , cd8 , t cell , bone marrow , signal transduction , phospholipase c , alpha (finance) , medicine , biology , endocrinology , immunology , cancer research , immune system , microbiology and biotechnology , tyrosine kinase , construct validity , nursing , patient satisfaction
It is controversial whether altered levels of TCR/CD3‐associated signalling molecules play a role in the T‐cell dysfunction of cancer patients. In multiple myeloma (MM), peripheral blood T (PBT) lymphocytes are functionally impaired by prolonged exposure to tumour cells, and so we investigated the organization of the TCR/CD3‐associated signal transduction machinery. The aim of this study was two‐fold: first, to investigate the levels of CD3ζ, p56 lck , p59 fyn , ZAP‐70, protein kinase C‐α (PKC‐α) and phospholipase C‐γ (PLC‐γ) in MM PBT cells; second, to determine whether levels of expression were correlated with clinical or prognostic factors. Forty‐four MM patients were studied and 25 age‐matched normal donors served as controls. On average, PKC‐α was the only significantly decreased ( P <0.001) signalling molecule, whereas levels of CD3ζ, p56 lck , p59 fyn , PLC‐γ and ZAP‐70 were not statistically different. However, there was wide variation between individual patients, and levels for each single protein also varied. A 75% or greater decrease in protein expression was observed, ranging from 8% (p59 fyn ) to 68% (PCK‐α) of MM patients. When patients were grouped according to the cut‐off values of prognostic factors such as the serum levels of C reactive protein (CRP), β2‐microglobulin (β2M), neopterin (NPT) and the labelling index (LI%) of bone marrow (BM) plasma cells, the only difference observed was the lower PKC‐α expression in patients with high serum NPT values. None of the T‐cell signalling molecule levels was affected by the duration of tumour exposure, calculated on the number of years and/or months that had elapsed since diagnosis, or by disease status. In conclusion, there was a significant decrease of PCK‐α in MM T cells; however, neither this decrease nor the heterogenous levels of the other T‐cell signalling molecules were clearly correlated with prognosis, duration of tumour exposure, and disease status.