Treatment of relapsing and refractory adult acute myeloid leukemia according to in vitro clonogenic leukemic cell drug sensitivity.

In an attempt to improve the results of treatment in patients with relapsing or refractory acute myeloid leukemia (AML), we conducted a pilot study using a two-drug salvage regimen according to the in vitro clonogenic leukemic cell (CFU-L) drug sensitivity. Fourteen patients were included in the study, 10 with relapsing and 4 with refractory AML. Drug exposure was assessed for daunorubicin, cytosine arabinoside, etoposide, mitoxantrone and amsacrine.

Cyclin A expression in human hematological malignancies: a new marker of cell proliferation.

Several in vitro studies have shown that the cyclin A gene is expressed and plays an important role in both the S and G2-M phases of the cell cycle. We analyzed cells from the blood and bone marrow of patients with various, mostly neoplastic, hematological disorders to determine whether (a) the cyclin A protein level correlated with that of cyclin A RNA and (b) cell distribution among the different phases of the cell cycle correlated with cyclin A RNA expression. Thirty-eight patients were studied by means of dot blot and Western blot techniques for cyclin A RNA and protein accumulation, and 21 were also studied for cell cycle distribution by using flow cytometric analysis.

Multidrug resistance (MDR) gene expression in acute non lymphoblastic leukemia: sequential analysis.

Sequential evaluation of P-glycoprotein expression was performed in 29 patients with acute nonlymphoblastic leukemia using immunocytochemistry with the C219 antibody. At diagnosis, 32% of the patients exhibited more than 5% of the P-gp(+) leukemic cells. Under chemotherapy, 62% of the patients eventually expressed a subset of P-gp positive leukemic cells.

Molecular analysis of 12 patients with the t(8;21) translocation and M2 acute myelogenous leukemia.

The t(8;21)(q22;q22) is a nonrandom cytogenetic abnormality associated with acute myelogenous leukemia of the M2 subtype (FAB classification). The 8q- and 21q+ derivative chromosomes have previously been isolated in somatic cell hybrids and used to map the anonymous sequences D21S65 and D21S17, which were proximal and distal, respectively, to the breakpoint on chromosome 21. DNA from a series of 12 t(8;21) patients and 7 controls was analyzed by pulsed field gel electrophoresis.

Relevance of mdr1 gene expression in acute myeloid leukemia and comparison of different diagnostic methods.

In an attempt to determine the incidence and clinical relevance of mdr1 gene expression in acute myeloid leukemia (AML), we examined 126 specimens obtained from adult patients with de novo AML by slot blot and immunocytochemistry. We found a high incidence of mdr1 gene expression in newly diagnosed patients (27% by immunocytochemistry and 43% by slot blot). No difference was observed between newly diagnosed patients and relapsed patients.

Prognostic value of in vitro uptake and retention of cytosine arabinoside in acute myelogenous leukemia.

In vitro uptake and retention of 3H-cytosine arabinoside (ara-C) was studied in 68 acute myelogenous leukemia (AML) patients (ten were studied twice) treated with a regimen containing conventional (54 patients) or high doses (24) of ara-C. Drug uptake and retention after four hours were measured following 30 minutes exposure to 1 and 50 micrograms/mL of ara-C. A good correlation was observed between high uptake in the acid soluble (AS) fraction (P less than .

Prognostic value of clonogenic assay for induction and duration of complete remission in acute myelogenous leukemia.

The validity of an in vitro clonogenic drug sensitivity assay to predict the induction and the duration of complete remission was evaluated in a group of 81 patients with acute myelogenous leukemia treated with chemotherapy including an anthracycline drug (daunorubicin or adriamycin) and cytosine arabinoside (Ara-C). The inhibition of bone marrow clonogenic leukemic cells by in vitro exposure to anthracyclines 10(-5) and 10(-6) M, Ara-C 10(-5) M, and daunorubicin 10(-6) M + Ara-C 10(-7) M was significantly correlated with the achievement of a complete remission, but not with the duration of remission. A high second plating efficiency was correlated with short duration of complete remission, reflecting the poor prognosis of a high self-renewal capacity.

DNA ligases in human leukemia.

Following partial purification on sucrose gradient and/or phosphocellulose chromatography, DNA ligase was tested in peripheral white blood and bone marrow cells of nearly 100 patients with various kinds of leukemias, mainly acute leukemias. Terminal deoxynucleotidyl transferase (TdT) was tested in parallel. DNA ligase of acute myeloblastic leukemia (AML) was extracted with the same sedimentation coefficient (5.