Idioma:

CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo

Reimer, Jana ; Knöß, Sabine ; Labuhn, Maurice ; Charpentier, Emmanuelle M ; Göhring, Gudrun ; Schlegelberger, Brigitte ; Klusmann, Jan-Henning ; Heckl, Dirk

Haematologica (Roma), 2017-09, Vol.102 (9), p.1558-1566 [Periódico revisado por pares]

Italy: Ferrata Storti Foundation

Texto completo disponível

Citações Citado por

Enviar para

Título:
CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo
Autor: Reimer, Jana ; Knöß, Sabine ; Labuhn, Maurice ; Charpentier, Emmanuelle M ; Göhring, Gudrun ; Schlegelberger, Brigitte ; Klusmann, Jan-Henning ; Heckl, Dirk
Assuntos: Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Cell Transformation, Neoplastic - pathology ; Cells, Cultured ; Chromosomes, Human, Pair 11 - genetics ; Chromosomes, Human, Pair 11 - metabolism ; Chromosomes, Human, Pair 19 - genetics ; Chromosomes, Human, Pair 19 - metabolism ; CRISPR-Cas Systems ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - pathology ; Humans ; Leukemia - genetics ; Leukemia - metabolism ; Leukemia - pathology ; Translocation, Genetic
É parte de: Haematologica (Roma), 2017-09, Vol.102 (9), p.1558-1566
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
J-HK and DH contributed equally to the manuscript
JR and SK contributed equally to the manuscript
Descrição: Chromosomal translocations that generate oncogenic fusion proteins are causative for most pediatric leukemias and frequently affect the gene. modeling of chromosomal translocations in human hematopoietic stem and progenitor cells is challenging but essential to determine their actual leukemogenic potential. We therefore developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34 hematopoietic stem and progenitor cells and induced the t(11;19)/MLL-ENL translocation. Leveraging this system, we could demonstrate that hematopoietic stem and progenitor cells harboring the translocation showed only a transient clonal growth advantage In contrast, t(11;19)/MLL-ENL-harboring CD34 hematopoietic stem and progenitor cells not only showed long-term engraftment in primary immunodeficient recipients, but t(11;19)/MLL-ENL also served as a first hit to initiate a monocytic leukemia-like disease. Interestingly, secondary recipients developed acute lymphoblastic leukemia with incomplete penetrance. These findings indicate that environmental cues not only contribute to the disease phenotype, but also to t(11;19)/MLL-ENL-mediated oncogenic transformation itself. Thus, by investigating the true chromosomal t(11;19) rearrangement in its natural genomic context, our study emphasizes the importance of environmental cues for the pathogenesis of pediatric leukemias, opening an avenue for novel treatment options.
Editor: Italy: Ferrata Storti Foundation
Idioma: Inglês

Links

Voltar para lista de resultados

Anterior Resultado 9 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo

Reimer, Jana ; Knöß, Sabine ; Labuhn, Maurice ; Charpentier, Emmanuelle M ; Göhring, Gudrun ; Schlegelberger, Brigitte ; Klusmann, Jan-Henning ; Heckl, Dirk

Italy: Ferrata Storti Foundation

Buscando em bases de dados remotas. Favor aguardar.