mitoguazone and Leukemia--Erythroblastic--Acute

A 62-year-old woman was diagnosed as having malignant lymphoma, diffuse large B-cell type. She underwent chemotherapy with the standard dose of CHOP and MINE regimens, resulting in complete remission. Four months later, the myelodysplastic syndrome of RA (refractory anemia) with pancytopenia developed and rapidly progressed to acute myelogenous leukemia (AML-M6) in 4 months. Cytogenetic analysis for the bone marrow specimens of both periods of MDS and AML-M6 revealed complex karyotypic abnormalities involving chromosome 5, 7, 11q23 and 20q11.2. Neither rearrangement of the MLL gene by Southern blot analysis nor tandem duplication of MLL gene by RT-PCR technique was detected. The patient was died from progression of leukemia and pneumonia. The autopsy showed no residual disease of lymphoma-related disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 5; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Leukemia, Erythroblastic, Acute; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mitoguazone; Myelodysplastic Syndromes; Neoplasms, Second Primary; Prednisolone; Vinblastine; Vincristine

The differentiation of murine erythroleukemic cells induced by hexamethylene bisacetamide is shown to be differently affected by two inhibitors of polyamine biosynthesis. Methyl glyoxal bis(guanyl hydrazone) (inhibitor or S-adenosyl methionine decarboxylase) inhibited this differentiation process. By using a novel experiment protocol the inhibitory effect of this drug on the induced differentiation was dissociated from pleiotropic effects on cell growth. Methyl glyoxal bis(guanyl hydrazone) only inhibited the induced differentiation if present during the first 6 h of culture of the cells with the inducer. No effect on the induced differentiation was observed if the drug was added to the culture medium 6 h after the inducer. alpha-Difluoro methylornithine (inhibitor of ornithine decarboxylase) stimulated the differentiation of these cells. Polyamine analysis demonstrated that alpha-difluoro methylornithine increased the rapidity and the amplitude of the changes in intracellular polyamines associated with this induced differentiation. The presence of methyl glyoxal bis(guanyl hydrazone) during the first 3 h with the inducer was sufficient to produce opposing changes in the intracellular polyamines. These results suggest that changes in either intracellular polyamines or the activities of polyamine biosynthetic enzymes play a regulatory role in the differentiation process induced in murine erythroleukemic cells by hexamethylene bisacetamide.

Topics: Acetamides; Animals; Cell Differentiation; Cell Division; Cell Line; Depression, Chemical; Eflornithine; Intracellular Fluid; Leukemia, Erythroblastic, Acute; Mice; Mitoguazone; Polyamines; Time Factors

Methylglyoxal bis(butylamidinohydrazone) (MGBB) inhibited S-adenosylmethionine decarboxylase (SAMDC) activity competitively with S-adenosylmethionine (SAM) showing the Ki value of 1.8 X 10(-5) M. MGBB showed less SAMDC-stabilizing effect in rat liver in vivo than did methylglyoxal bis-(guanylhydrazone) (MGBG). MGBB inhibited the growth of human erythroid leukemia K 562 cells. Putrescine, spermidine and spermine concentrations in MGBB-treated cells were depressed to 56%, 58% and 88% of the values of control cells, respectively. [35S]Methionine incorporation into trichloroacetic acid-insoluble fraction was decreased in the inhibitor-treated cells.

Topics: Adenosylmethionine Decarboxylase; Animals; Carboxy-Lyases; Cell Line; Humans; Leukemia, Erythroblastic, Acute; Liver; Male; Mitoguazone; Polyamines; Rats; Rats, Inbred Strains