MLL-AF9 leukemia stem cells: hardwired or taking cues from the microenvironment?
MLL rearrangements in humans lead to both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). While AML has been successfully produced in mice, modeling ALL has been more difficult. In this issue of Cancer Cell, Wei et al. (2008) describe generation of AML, ALL, and biphenotypic leukemia by manipulating the cytokine milieu of human progenitor cells expressing MLL-AF9. They demonstrate that both multipotent and lineage-restricted progenitors are targeted by MLL-AF9 fusion proteins and that Rac signaling is crucial for survival. This study demonstrates the heterogeneity of MLL-AF9 leukemic stem cells and the importance of the microenvironment in determining lineage outcome.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Andrew G
AG
Muntean
Jay L
JL
Hess
D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D019070:Cell Lineage; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004777:Environment; D053686:Fetal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D039902:Multipotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D013997:Time Factors; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D020744:rac GTP-Binding Proteins