RESUMO
The AML1 gene, located at chromosome 21q22, encodes a component (CBFalpha2) of a heterodimeric transcription factor complex termed core binding factor (CBF), which binds to DNA and activates gene expression. Chromosomal rearrangements may lead to disruption of this gene and development of acute leukemia. Twelve AML1 translocations have been identified to date, and include sites on chromosomes 1, 2, 3, 5, 8, 12, 14, 15, 16, 17, 18, and 19. Here we report two new translocations involving AML1 in acute myeloid leukemia, in which the disruption of the AML1 gene was documented by GTG banding cytogenetic studies and metaphase and interphase FISH analysis. These chromosomal breakpoints identified as harboring new fusion partners for AML1 are at 2p11.2 and 20q13.1. The two patients in who these translocation were identified were elderly males with newly diagnosed AML. These patients shared the same poor outcomes reported for other rare AML1 translocations.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas , Fatores de Transcrição/genética , Translocação Genética , Doença Aguda , Idoso , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 21/genética , Subunidade alfa 2 de Fator de Ligação ao Core , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide/genética , Leucemia Mieloide/patologia , MasculinoRESUMO
Using a recently developed hepsulfam-induced pancytopenia model in rhesus macaques, we have studied the effects of recombinant human interleukin-6 (rhIL-6) and rhIL-3 on marrow regeneration. Control animals were given hepsulfam (1.5 g/m2 by a single 30-minute intravenous [i.v.] injection, n = 4), while study animals received hepsulfam followed by rhIL-6, rhIL-3, or a combination of rhIL-6 and rhIL-3 (n = 3 per study group). Each cytokine was administered by once-daily subcutaneous (SC) injection (15 micrograms/kg/d) for 3 weeks beginning the day after chemotherapy (days 2 through 22). Mean platelet counts in control animals were < 100,000/microL on days 15 through 24, with 50% of the counts < 50,000/microL and two of four animals requiring platelet transfusion. In the rhIL-6- and rhIL-6/rhIL-3-treated groups, the nadir mean platelet counts were 164,000 +/- 58,700/microL and 162,300 +/- 23,800/microL, respectively, and occurred on day 15. Platelet counts in the rhIL-3-treated group were similar to those in controls. Mean absolute neutrophil counts (ANCs) < 1,000/microL occurred on days 10 through 29 in control animals, days 8 through 15 in rhIL-6-treated animals, and days 6 through 8 and 13 in rhIL-6/rhIL-3-treated animals. The frequency of ANCs < 500/microL was significantly less in the rhIL-6- and rhIL-6/rhIL-3-treated groups versus control groups (2.7 +/- 0.6 and 2.0 +/- 1.0 vs 7.0 +/- 1.4 occurrences, respectively; P < .05). rhIL-3-treated animals had ANCs similar to those in controls; one animal died with septicemia on day 21. Monkeys receiving rhIL-6 were significantly more anemic during the cytokine administration period; however, the anemia resolved by day 24. Coadministration of rhIL-3 and rhIL-6 partially corrected the anemia. The data indicate that rhIL-6 prevents significant thrombocytopenia and shortens the neutropenic period in this chemotherapy model.
