FLOW CYTOMETRIC ASSESSMENT OF MULTIDRUG-RESISTANCE (MDR) PHENOTYPE INACUTE MYELOID-LEUKEMIA

Forty one patients with acute myeloid leukemia (AML), including 27 at presentation and 14 relapsed or resistant cases, were assessed for lab oratory evidence of the MDR phenotype. Leukaemic cells from all 41 cas es were studied by immunocytochemistry using the JSB-1 monoclonal anti body and simultaneously by reverse transcription polymerase chain reac tion (RT-PCR) to evaluate expression of the mdr 1 gene. Cells from 32/ 41 cases were also assessed for daunorubicin (DNR) accumulation and re tention by flow cytometry (FC). Nineteen of the 41 (46%) patients were positive for MDR by JSB-1 immunocytochemistry (11/27 [41%] at present ation and 8/14 [57%] relapsed or resistant cases). Nine of the 19 (47% ) P-gp positive, de novo patients achieved complete remission. 22 pati ents were negative by JSB-1 immunocytochemistry (16/27 [59%] at presen tation and 6/14 [43%] of the relapsed or resistant cases) and 11/22 (5 0%) P-gp negative patients achieved a complete remission. Of the 32 pa tients assessed by FC, 7 (22%) were positive for the MDR phenotype wit h increased DNR accumulation and retention in the presence of the MDR reversing agent verapamil (VPM). 6/7 of the FC positive cases were als o JSB-1 positive, and 6 had additional poor risk features. Of the twen ty five FC negative patients, 6 had received previous chemotherapy and 15 (60%) achieved complete remission. Mdr 1 mRNA levels were increase d in all seven FC positive cases whereas only 7/19 JSB-1 positive case s had raised mdr 1 mRNA levels. These results suggest that the assessm ent of MDR status by immunocytochemistry using JSB-1 is not predictive of response to chemotherapy. Flow cytometric analysis of blast cells appears to correlate well with mdr 1 mRNA levels and may be a better p redictor of treatment outcome.