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					  Regulation of myeloid leukaemia by the cell-fate determinant Musashi
                           Nature 466, 765–768, August 5, 2010

Takahiro Ito, Hyog Young Kwon, Bryan Zimdahl, Kendra L. Congdon, Jordan Blum,
William E. Lento, Chen Zhao1, Anand Lagoo, Gareth Gerrard, Letizia Foroni, John
Goldman, Harriet Goh, Soo-Hyun Kim, Dong-Wook Kim, Charles Chuah, Vivian G.
Oehler, Jerald P. Radich, Craig T. Jordan & Tannishtha Reya

                                                             指導教授:孫德珊 老師
                                                             講評老師:陳紀雄 老師


     Chronic myelogenous leukaemia (CML) can progress from chronic phase to an
aggressive blast crisis phase, with loss of the capacity to differentiation, but the molecular
mechanisms that underlie this transition remain unclear. Numb is known as a
membrane-bound protein that has a role in determining binary cell fates during
development. In this study, authors found that Numb was expressed at lower levels in the
blast crisis phase than the chronic phase, and that ectopic expression of Numb promoted
differentiation and inhibited CML progression in vivo. In previous study showed that the
RNA-binding protein Musashi (Msi) could repress Numb. Authors showed that the
expression of Msi2 was higher in the blast crisis CML. Specially, loss of Msi2 restored the
expression of Numb and impaired leukemia growth and progression in vitro and in vivo.
Finally, authors found a marked upregulation of MSI2 in patient during CML progression,
and increased MSI2 expression was not only associated with higher risk of relapse but also
with higher risk of death. Together, these data indicated that Musashi-Numb pathway as an
important regulator of myeloid leukaemia and that targeting it may provide a new approach
to therapy.

1. Calabretta, B. & Perrotti, D. The biology of CML blast crisis. Blood 103, 4010–4022
2. Dash, A. B. et al. A murine model of CML blast crisis induced by cooperation between
   BCR/ABL and NUP98/HOXA9. Proc. Natl Acad. Sci. USA 99, 7622–7627 (2002).
3. Melo, J. V. & Barnes, D. J. Chronic myeloid leukaemia as a model of disease evolution
   in human cancer. Nature Rev. Cancer 7, 441–453 (2007).

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