Publication

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

Rizo, A., Horton, S. J., Olthof, S., Dontje, B., Ausema, A., van Os, R., van den Boom, V., Vellenga, E., de Haan, G. & Schuringa, J. J., 25-Nov-2010, In : Blood. 116, 22, p. 4621-4630 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

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)

Original languageEnglish
Pages (from-to)4621-4630
Number of pages10
JournalBlood
Volume116
Issue number22
Publication statusPublished - 25-Nov-2010

    Keywords

  • CHRONIC MYELOID-LEUKEMIA, CHRONIC MYELOGENOUS LEUKEMIA, HEMATOPOIETIC STEM-CELLS, ACUTE LYMPHOBLASTIC-LEUKEMIA, IMPAIRS SELF-RENEWAL, MYELOPROLIFERATIVE DISEASE, PHILADELPHIA-CHROMOSOME, STEM/PROGENITOR CELLS, IMMUNODEFICIENT MICE, ENFORCED EXPRESSION

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