Prognostic Value of P-Glycoprotein and Leukocyte Differentiation Antigens in Chronic Myeloid Leukemia

Abstract

P-glycoprotein (Pgp) mediated multidrug resistance is often the cause of therapy failure in some tumors. Pgp expression was shown to have prognostic value in several hematological malignancies, especially in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL). In chronic myeloid leukemia (CML) Pgp is expressed by peripheral blood (PB) cells more often in the terminal disease stages (20-50% of patients have Pgp+ phenotype). Sequential studies show that Pgp+ cells often disappear from the PB during the course of therapy. Nevertheless Pgp expression has some prognostic value in blast crisis (BC) predicting shorter BC, while CD13 has the same predictive value in BC. 10% of patients formed a distinct group with large numbers of Pgp+CD34+ blasts in the PB and also had shorter BC. Cases with inactive Pgp were found in chronic and accelerated phases of CML but not in BC.

Cells from chronic myelogenous leukaemia patients at presentation exhibit multidrug resistance not mediated by either MDR1 or MRP1

“…TMR and doxorubicin uptake into the cells was not modulated by inhibitors of either MDR1 or MRP1, thus indicating that, at least, ex‐vivo neither MDR1 nor MRP1 mediate the energy‐dependent exclusion of drugs from these cells. This confirms the report by Stavrovskaya et al (1998) on MDR1 functional activity in the peripheral blood of 12 patients in chronic phase and five patients in accelerated phase. None of these patients showed MDR1 activity, measured as rhodamine‐123 efflux sensitive to known MDR1 inhibitors (e.g.…”

Revisiting the ABCs of Multidrug Resistance in Cancer Chemotherapy

“…For example, it has been shown that ABCB1 expression can range from 0-100% in the chronic phase (CP) in CML patients [76,[162][163][164][165][166][167][168]. Several groups have reported that ABCB1 expression is higher in the blastic phase than the chronic phase [162,164,[167][168][169]. In contrast, other studies in CML patients have shown no significant difference of ABCB1 expression between the chronic and blastic phase [76,163,170].…”

Functional consequence of MDR1 expression on imatinib intracellular concentrations

“…8,9 These findings should stimulate further research to evaluate the addition of Pgp inhibitors to imatinib for the treatment of CML blastic crisis. …”