Naslov
Individual follow up of P-glycoprotein activity : A valuable tool in the definition of the overall management strategy for MM patients

Autori
Majdak, Patricia ; Ajduković, Radmila ; Bendelja, Krešo ; Svoboda-Beusan, Ivna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the ..... ; u: Haematologica 90 (2005) (S2) / - , 2005, 425-425

Mjesto i datum
,

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
multiple myeloma; multidrug resistance; Pgp

Sažetak
Background. Multiple myeloma (MM)is a disease where we would like to know the future: some patients present early with a heavy form of the disease needing an aggressive therapy, or transplantation, while others live for years after the diagnosis without any of the symptoms. During this time, we wait for the first symptoms to start the treatment, knowing that the most favorable outcome have those patients who achieve a complete or near complete remission following the first therapy, before the development of chemoresistance associated with the relapse of MM following an initial responsivenesss to chemotherapy, and with the incurability of MM and overall poor prognosis for the patient. All the research on MM so far couldn't elucidate what makes MM behave in specific manner: a key event in the development of the disease, or an intrinsic characteristic of the patient. While the quest for answer continues, also in the realm of genetic polymorphysm, we would like to remind that individual follow-up of P-glycoprotein (P-gp), the first multidrug resistance (MDR) protein discovered, can help in the overall follow-up of the MM patient, and give us a hand in the therapeutic management of the individual MM patient. Aims. Previous studies have suggested an association beteen the increase of expression/activity of P-gp and the development of MDR chemoresistance and relapse of MM. Still, due to a relative small number of patients, sample size, of the single studies for the individual variability of the constitutive expression of P-gp, and as seen lately, the polymorphism of the P-gp encoding MDR1 gene, no clear cut conclusions and recommendations regarding MDR proteins were made. Here we would like to present a long-term follow up of a patient with MM from the diagnosis through the relapse into the remission, highlighting the influence of therapy protocols on the change of activity of p-gp. Methods. The standard flow-cytometric Rhodamine 123 (Rh123) dye functional efflux assay with Cyclosporine A (CsA) as the P-gp modulator has been used, and the P-gp activiry expressed as the ratio of mean fluorescence (RMF) with and without the use of CsA. Results: i)P-gp activity acts in response to treatment i.e. change in therapy, irrelevant of the initial/constitutive level of P-gp activity. ii) P-gp activity increases with the use of the MDR therapy protocols. iii) Steady P-gp activity increase is concurrent with poor response observed on the clinical level.Conclusions. P-gp activity is an intrinsic characteristic of an individual, and needs to be individually monitored to allow for any inference. If individually monitored, P-gp activity can have a prognostic value regarding response to therapy of MM. As almost all patients with MM will relapse, the individual follow-up of P-gp activity can be a valuable tool in the definition of the overall management strategy and planing of the treatment of relapse for MM patients.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA