BMI1 collaborates with BCR-ABL in leukemic transformation of human CD34(+) cells

Aleksandra Rizo, Sarah J. Horton, Sandra Olthof, Bert Dontje, Albertina Ausema, Ronald van Os, Vincent van den Boom, Edo Vellenga, Gerald de Haan, Jan Jacob Schuringa*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

58 Citaten (Scopus)

Samenvatting

The major limitation for the development of curative cancer therapies has been an incomplete understanding of the molecular mechanisms driving cancer progression. Human models to study the development and progression of chronic myeloid leukemia (CML) have not been established. Here, we show that BMI1 collaborates with BCR-ABL in inducing a fatal leukemia in nonobese diabetic/severe combined immunodeficiency mice transplanted with transduced human CD34(+) cells within 4-5 months. The leukemias were transplantable into secondary recipients with a shortened latency of 8-12 weeks. Clonal analysis revealed that similar clones initiated leukemia in primary and secondary mice. In vivo, transformation was biased toward a lymphoid blast crisis, and in vitro, myeloid as well as lymphoid long-term, self-renewing cultures could be established. Retroviral introduction of BMI1 in primary chronicphase CD34(+) cells from CML patients elevated their proliferative capacity and self-renewal properties. Thus, our data identify BMI1 as a potential therapeutic target in CML. (Blood. 2010; 116(22): 4621-4630)

Originele taal-2English
Pagina's (van-tot)4621-4630
Aantal pagina's10
TijdschriftBlood
Volume116
Nummer van het tijdschrift22
DOI's
StatusPublished - 25-nov-2010

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