RESUMO
We examined the MLL translocation in two cases of infant AML with X chromosome disruption. The G-banded karyotype in the first case suggested t(X;3)(q22;p21)ins(X;11)(q22;q13q25). Southern blot analysis showed one MLL rearrangement. Panhandle PCR approaches were used to identify the MLL fusion transcript and MLL genomic breakpoint junction. SEPTIN6 from chromosome band Xq24 was the partner gene of MLL. MLL exon 7 was joined in-frame to SEPTIN6 exon 2 in the fusion transcript. The MLL genomic breakpoint was in intron 7; the SEPTIN6 genomic breakpoint was in intron 1. Spectral karyotyping revealed a complex rearrangement disrupting band 11q23. FISH with a probe for MLL confirmed MLL involvement and showed that the MLL-SEPTIN6 junction was on the der(X). The MLL genomic breakpoint was a functional DNA topoisomerase II cleavage site in an in vitro assay. In the second case, the karyotype revealed t(X;11)(q22;q23). Southern blot analysis showed two MLL rearrangements. cDNA panhandle PCR detected a transcript fusing MLL exon 8 in-frame to SEPTIN6 exon 2. MLL and SEPTIN6 are vulnerable to damage to form recurrent translocations in infant AML. Identification of SEPTIN6 and the SEPTIN family members hCDCrel and MSF as partner genes of MLL suggests a common pathway to leukaemogenesis.
Assuntos
Cromossomos Humanos Par 11/genética , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação ao GTP/genética , Leucemia Mieloide/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética/genética , Cromossomo X/genética , Doença Aguda , Sequência de Bases , Quebra Cromossômica/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 3/genética , Proteínas do Citoesqueleto , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Lactente , Leucemia Mielomonocítica Aguda/genética , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , SeptinasRESUMO
We report the case of a 7-year-old boy with Fanconi's anemia, who underwent a bone marrow transplant using an unrelated donor, and who received an inadvertent dose of cytarabine (cytosine arabinoside). The cytarabine was given by mistake 6 months following transplant. This caused excessive toxicity to many systems, including the pulmonary and renal systems. The patient recovered from the episode, but this article further highlights the acute adverse effects of cytarabine. Furthermore, it is the first report of excessive toxicity to cytarabine in a child with Fanconi's anemia. The article also highlights the problems of medication administration errors, particularly in those exquisitely sensitive to the effects of toxic drugs.
