Prognostic value of apoptosis of tumor clone bone marrow cells in patients with multiple myeloma
Zhanna V. Chubukina, Ludmila N. Bubnova, Stanislav S. Bessmeltsev
Russian Research Institute of Hematology and Transfusiology, St. Petersburg, Russia
Summary
Purpose
To study the apoptosis of tumor cells (plasma cells, PC) in bone marrow of patients with multiple myeloma (MM) and to evaluate the possibility of using this parameter as a predictor of treatment efficacy.
Materials and Methods
The study comprised 34 patients with active stage MM. Myelogram: PC 11.4–86.4 %. Apoptosis of PC was detected by binding Annexin V-FITC with a membrane marker of early apoptosis–phosphatidylserine. The analysis was performed using the Flow Cytometer “Cytomics FC 500 Beckman Coulter”, USA. Apoptosis of PC was evaluated before and after a course of specific therapy.
Results
It was demonstrated that initially spontaneous apoptosis of PC in all MM patients was on average 25.4 ± 3.3%. But in 32% (11) of patients apoptosis was significantly lower than average (15.6 ± 2.9%),while in 68% (23) of patients PC apoptosis was significantly higher than average (35.2 ± 3.0%). After treatment there was a 2.5-fold (39.1 ± 4.1%) increase of apoptosis index in those patients with an initial decrease. This coincided with an occurrence of clinical–hematological remission in this group. In patients with a higher initial spontaneous apoptosis, its increase had not been noted in any case (34.6 ± 2.8%), and clinical therapeutic effect was also absent.
Conclusion
Initially decreased apoptosis of bone marrow PC is a predictor of a more favorable course of disease and of therapeutic efficacy. On the contrary, a higher level on initial spontaneous PC apoptosis is prognostically an unfavorable marker, because tumor cells remain refractory to chemotherapy and the induction of the apoptotic process is insufficient.
Keywords
multiple myeloma, apoptosis, plasma cells
