Mixed up | Nature Reviews Cancer

Access through your institution Buy or subscribe The authors used MA9 cells — CD34+ human cord blood (CB) cells transduced with an _MLL–AF9_ construct — and showed that they are immortal and

can be cultured to assume either myeloid or lymphoid phenotypes, highlighting the contribution of culture conditions in lineage determination. When injected into non-obese diabetic, severe

combined immunodeficient (NS) mice, MA9 cells led to the development of both AML and ALL. However, the introduction of MA9 cells into transgenic NS mice that express the human cytokines stem

cell factor, granulocyte-macrophage colony-stimulating factor and interleukin 3 not only biased the disease towards a myeloid phenotype, but resulted in a more aggressive disease, further

reinforcing the role of the cytokine milieu in specifying lineage. To further understand the nature of the LSC in _MLL–AF9_ leukaemias, myeloid and lymphoid lines derived from a single CB

transduction were injected into β2-globulin-deficient NS mice, triggering the development of AML and ALL respectively. Intriguingly, clonal identity was confirmed between at least one case

of AML and ALL, implying that an LSC can be multipotent and can promote expansion of both myeloid and lymphoid lineages, and the subsequent development of two phenotypically diverse

diseases. However, further experiments established that lineage-restricted LSCs can also be targets for MLL–AF9, thus demonstrating heterogeneity within LSCs in mixed-lineage leukaemia. This

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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH PAPER * Wei, J. et al.

Microenvironment determines lineage fate in a human model of _MLL–AF9_ leukemia. _Cancer Cell_ 13, 483–495 (2008) Article  CAS  Google Scholar  Download references Authors * Safia Ali Danovi

View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Danovi, S. Mixed

up. _Nat Rev Cancer_ 8, 568–569 (2008). https://doi.org/10.1038/nrc2445 Download citation * Published: 03 July 2008 * Issue Date: August 2008 * DOI: https://doi.org/10.1038/nrc2445 SHARE

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