News Release

An excess of healthy cells holds leukemia in check

Peer-Reviewed Publication

JCI Journals

The NF1 gene encodes the tumor suppressor Neurofibromin 1, so named because of its effects on cells in the CNS, but myeloid cells with NF1 mutations are also prone to uncontrolled growth. In one useful model of juvenile myelomonocytic leukemia (JMML), lethally irradiated mice receive hematopoietic cells from the liver of a fetal mouse lacking this growth-inhibiting protein. Although this protocol reliably yields overgrowth by mutant monocytes, Zhang and colleagues note that it is highly artificial, since leukemic cells would more typically arise as a minor population within a large number of normal cells. Testing the population dynamics in a more realistic setting, the authors show that the NF1 mutation provides the cells only a limited growth advantage that depends on the cell’s genetic background. In addition, although NF1–/– liver cells can also yield fast-growing lymphoid cells, lymphocytic leukemias are not seen, either in recipient animals or in JMML families carrying an NF1 mutation. In the case of the myeloid lineage, when NF1 deficient cells are present below a threshold number, they outgrow normal cells for only a limited period, after which they represent a stable population for a period of months. Some additional event must therefore be required if the cells are to grow out of control after achieving this pattern of stable chimerism. The finding raises troubling questions about experiments modeling tumor growth using a homogeneous source of tumor-prone cells.

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