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Science 18 February 2005:
Vol. 307. no. 5712, pp. 1101 - 1104
DOI: 10.1126/science.1106114
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Reports

Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells

Joseph T. Opferman,1,2* Hiromi Iwasaki,2 Christy C. Ong,1,2 Heikyung Suh,1,2 Shin-ichi Mizuno,2 Koichi Akashi,2{dagger} Stanley J. Korsmeyer1,2{dagger}

Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia–1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.

1 Howard Hughes Medical Institute, Department of Cancer Immunology and AIDS, Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
2 Dana Farber Cancer Institute, Department of Cancer Immunology and AIDS, Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.

* Present address: Department of Biochemistry, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.

{dagger} To whom correspondence should be addressed. E-mail: Koichi_Akashi{at}dfci.harvard.edu (K.A.); Stanley_Korsmeyer{at}dfci.harvard.edu (S.K.)

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