Retroviral activation ofEvi-l gene expression is one of the most common transforming events in murine myeloid leukemias. To evaluate the role of the EVII gene in human acute myelogenous leukemia (AML), leukemic blasts or cell lines from 116 patients were examined. In eight patients the EVII gene was expressed and all but one had cytogenetically detectable translocations of chromosome 3q26 where the EVII gene has been localized. To identify breakpoints, a restriction map that spans 1700 kilobases (kb) of the EVII locus was developed by pulsed-field gel electrophoresis. In one case, t(3;3)(q21;q26), a rearrangement was localized to 170-330 kb 5' of the gene. In a second case, t(3;3)(q21;q26), there was a rearrangement 13 kb 5' of the gene. This rearrangement was cloned and shown to be due to the fusion of sequences from 3q21-22 with the EVII locus. In the third case, ins(3)-(q21q25q27), there was a rearrangement that mapped 150 kb downstream from the 5' end of the gene.Human acute myelogenous leukemia (AML) is associated with a number of recurring chromosomal abnormalities. Only recently have the genes associated with these cytogenetic changes been identified. One region of recurring abnormalities involves chromosome band 3q26 and includes t(3;3)(q21 ;q26), inv(3)(q21q26), t(2;3)(p21 ;q26), t(3;21)(q26;q22), and t(3 ;5)(q25

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A liquid culture technique was used to study 23 in inflammatory SF, with tritiated thymidine uptake of 3,501±1,140 cpm in the presence of RA samples (n = 15) compared to 1,985±628 for non-RA inflammatory SF (n = 7) (P < 0.05) and 583±525 for medium (n = 6) (P < 0.01). The

Illudins are potent natural products derived from Omphalotus illudens and related fungi. The chemical structure of illudins differs from that of other conventional chemotherapeutic agents. While illudins are toxic to most tumor cells after prolonged exposure (greater than or equal to 48 hr), with shorter exposure times (less than or equal to 2 hr), they show selective toxicity for human myelocytic leukemia and epidermoid, lung, ovarian, and breast carcinoma cells of various species of origin. The apparent histologic specificity of illudin S toxicity is based on an energy-dependent transport mechanism present in sensitive cells, but absent in cells relatively resistant to illudin S. For human myeloid leukemia HL60 cells, the Michaelis constant was 4.2 microM and the maximum velocity was 12.2 pmol/minute per 10 million cells or 730 pmol/hour per 10 million cells. The energy-dependent transport mechanism was detected in other mammalian tumor cells.

Reaction of the fungal sesquiterpene illudin S with excess paraformaldehyde in dilute H2SO4 gives (hydroxymethyl)acylfulvene. The primary allylic hydroxyl thus formed can undergo very facile replacement by a variety of nucleophiles. (Hydroxymethyl)acylfulvene (MGI.114) was more toxic than a precursor, acylfulvene, but less toxic than the parent compound illudin S to HL 60 cells.