RESUMO
ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Here, we report the case of a 16-year-old male diagnosed with a MPN, 7 months post-completion of treatment for Burkitt leukaemia. RNA sequencing analysis confirmed the presence of an ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine-kinase domain. Of note, secondary ETV6-ABL1-rearranged neoplastic diseases have not been reported to date. The patient was started on a tyrosine kinase inhibitor (TKI; imatinib) and, subsequently, underwent a 10/10 matched unrelated haematopoietic stem cell transplant. He is disease-free five years post-transplant. Definitive evidence of the prognostic influence of the ETV6-ABL1 fusion in haematological neoplasms is lacking; however, overall data suggest that it is a poor prognostic factor, particularly in patients with ALL and AML. The presence of this ETV6-ABL1 fusion should be more routinely investigated, especially in patients with a CML-like picture. More routine use of whole-genome and RNA sequencing analyses in clinical diagnostic care, in conjunction with conventional cytogenetics, will facilitate these investigations.
Assuntos
Linfoma de Burkitt , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Proteínas Tirosina Quinases/genética , Hibridização in Situ Fluorescente , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Chromosomal rearrangements resulting in fusion transcripts have been reported in precursor B-cell acute lymphoblastic leukemia (B-ALL). The identification of fusion events is crucial in the diagnosis of B-ALL. In this study, we used NanoString nCounter technology to design, validate, and evaluate a multiplex panel for the detection of B-ALL fusion transcripts. Fifty-one B-ALL fusion transcripts reported in children in the literature were included in the design of the NanoString panel. Twenty-six fusion transcripts were validated using 64 positive-control samples and 74 negative-control samples with 100% sensitivity and 99% specificity in comparison to RT-PCR. Our results support a potential role of NanoString's technology as a robust and cost-effective technique that could be used in the detection of fusion transcripts and implemented into the diagnostic algorithm of B-ALL.
Assuntos
Nanotecnologia/métodos , Proteínas de Fusão Oncogênica/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Biomarcadores Tumorais/sangue , Medula Óssea , Linhagem Celular Tumoral , Criança , Aberrações Cromossômicas , Humanos , Nanotecnologia/economia , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
We describe a unique case of de novo childhood acute myeloid leukemia in which the blasts showed evidence of hemophagocytosis and harbored inv(8) (p11q13) chromosomal abnormality. Reverse-transcription polymerase chain reaction showed the presence of 2 MOZ-TIF2 fusion transcripts. To our knowledge, this is the eighth overall and the fourth childhood case of acute myeloid leukemia with inv(8) (p11q13) with MOZ-TIF2 fusion.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 11/genética , Leucemia Mieloide/genética , Linfo-Histiocitose Hemofagocítica/genética , Proteínas de Fusão Oncogênica/genética , Doença Aguda , Criança , Feminino , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/patologia , Transcrição GênicaAssuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 4/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética/genética , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Resultado do TratamentoRESUMO
In this report, we studied DHX32 expression in human Jurkat T cells. Co-stimulation of CD3 and CD28 resulted in upregulation of DHX32. No significant changes in the expression of the closely related RNA helicases were seen. Ionomycin treatment alone was sufficient to upregulate the expression of DHX32 mRNA isoform transcribed from the proximal promoter. We cloned DHX32 proximal promoter and identified a 218bp fragment containing two potential binding sites for the transcription factor nuclear factor of activated T cells (NF-AT). Mutation of core sequence of NF-AT resulted in reduced transcriptional activity, with more reduction observed in the second NF-AT site. Electrophoretic mobility shift assay results were consistent with a specific binding of NF-AT from ionomycin stimulated nuclear extract of Jurkat cells to oligonucleotide probes from DHX32 proximal promoter. These results suggest that the DHX32 expression is modulated in Jurkat T cells via a pathway that involves NF-AT.
