OBJECTIVES:
I. Determine Pgp antigen expression and Pgp-mediated functional multidrug resistance (MDR) in pretreatment acute myeloid leukemia (AML) cells from adult patients enrolled on CALGB clinical trials of PSC-833 Pgp modulation.
II. Correlate Pgp-mediated MDR with patient pretreatment characteristics including age, immunophenotype, and karyotype.
III. Correlate Pgp expression, function, and in vitro modulation by PSC-833 with treatment outcome in previously untreated AML patients treated on CALGB Pgp modulation trials.
IV. Determine Pgp expression and function in AML cells from patients with refractory or relapsed leukemia following induction chemotherapy administered with or without PSC-833.
V. Correlate acquisition of drug resistance with changes in expression of other antigens and gain or loss of leukemic populations at relapse in these patients.
VI. Determine the role of other mediators, including multidrug resistance-associated protein (MRP) and lung-resistance protein (LRP), in mediating MDR in these patients at diagnosis and with relapsed or refractory disease after induction chemotherapy with or without PSC-833.
VII. Determine the frequency of Pgp-, MRP-, and LRP- mediated MDR in adult acute lymphoblastic leukemia cells and correlate this frequency with pretreatment characteristics and treatment outcome in these patients.
OUTLINE:
Samples are obtained: 1) pretreatment, 2) at the time of documentation of refractory disease in acute myeloid leukemia (AML) patients who do not achieve complete response (CR) after induction therapy, and 3) at the time of first relapse in patients who achieve CR.
Marrow cells are preferentially used for all samples, but peripheral blood is acceptable if marrow is not available and the blood contains 20% or more blasts. Pgp expression is measured using flow cytometry. AML samples are analyzed by immunoenzyme techniques (IET) using antibodies to CD33, CD34, and MRK16. B-lineage acute lymphoblastic leukemia (ALL) samples are analyzed by IET using antibodies to CD19, CD34, and MRK16. The antibodies used to analyze T-cells include CD7 and CD34. Pgp function is measured by growing cells in the presence of PSC-833 in vitro and then measuring Pgp expression as above. Multidrug resistance-associated protein (MRP) is measured using IET with the MRPm6 antibody. Lung-resistance protein (LRP) is measured with IET and the LRP56 antibody. These results are correlated with flow cytometry results.
