MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice

Publication

MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice

Journal Paper/Review - Feb 1, 2003

So Chi Wai, Karsunky Holger, Passegué Emmanuelle, Cozzio Antonio, Weissman Irving L, Cleary Michael L

Units

Dermatologie | Venerologie | Allergologie

PubMed

12620410

Citation

So C, Karsunky H, Passegué E, Cozzio A, Weissman I, Cleary M. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 2003; 3:161-71.

Type

Journal Paper/Review (English)

Journal

Cancer Cell 2003; 3

Publication Date

Feb 1, 2003

Issn Print

1535-6108

Pages

161-71

Brief description/objective

A specific association with mixed lineage leukemias suggests that MLL oncoproteins may selectively target early multipotent hematopoietic progenitors or stem cells. We demonstrate here that a representative MLL fusion protein, MLL-GAS7, impairs the differentiation and enhances the in vitro growth of murine hematopoietic cells with multipotent features. The multilineage differentiation potential of these cells was suggested by their immuno-phenotypes and transcriptional programs and confirmed by their ability to induce three pathologically distinct leukemias in mice, including an acute biphenotypic leukemia (ABL) that recapitulates the distinctive hallmark features of many MLL-associated leukemias in humans. This experimental modeling of ABL in mice highlights its origin from multipotential progenitors that arrest at a bipotential stage specifically targeted or induced by MLL oncogenes.