HIF-1 can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.

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1 HIF-1 can act as a tumor suppressor gene in murine Acute Myeloid Leukemia. Velasco, Talia; Hyrenius Wittsten, Axel; Rehn, Matilda; Bryder, David; Cammenga, Jörg Published in: Blood DOI: /blood Link to publication Citation for published version (APA): Velasco, T., Hyrenius Wittsten, A., Rehn, M., Bryder, D., & Cammenga, J. (14). HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia. Blood, 124(24), DOI: /blood General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. L UNDUNI VERS I TY PO Box L und Download date: 17. Feb. 19

2 α ƒ ƒ ƒ ƒ Ž ƒ ƒž ƒ Žƒ ƒ œ š Ž ƒ Ž ƒ Š ƒ ƒ Ú ƒ ƒ ƒ ˆ Ž Žƒ ƒ Š ƒ ŽŽ ƒ ˆ Ž ƒ ƒ ˆ ƒ Ž ƒ ƒž Ž Ž ˆ α Š Ž ƒ Ú ƒ ƒ ƒ ˆ Ž Žƒ ƒ Š ƒ ŽŽ ÚŽ ƒ ƒ ƒ Ž Œ ƒ ƒ Ž Ž ƒš ƒ š ˆ ˆ ˆ d

3 ƒ ƒ ƒ ƒ ƒ Ž ƒ α Šƒ α ˆ ƒ Ž ƒ Ž ƒ ƒ Žˆ ƒž ˆŠ ƒ ŽŽ ƒ Ž ƒ ƒ ŽŽ Šƒ ˆŽ Ž š Š š ƒ Š ƒž Žƒ Š ŽŽ Žƒ Ž ƒž œƒ Š ƒ Š ƒ ˆŽ š ˆƒ Š ƒ Ž œƒ ˆŠ š ƒ Ž ˆƒ Š Š α ƒ ƒ ƒ Š ƒ ƒ Š ƒ ˆ Ž ƒž ƒ ƒ Šƒ Š ˆˆ Ž ƒ Š Ž ˆ α ƒ Ž Ž ƒ ƒ ƒ Žˆ ƒž ˆ š Ž ˆƒ Ž ƒ Žƒ ˆ ƒ Ž ˆ Š ƒ ŽŽ Žƒ ˆ α ƒ Ž ˆ ˆ α Ž ˆƒ Ž ˆ Š ƒ ƒ ƒ Šƒ Ž ƒ Š ˆ Š ƒ Ž Ž Š ˆ ƒ ƒ ƒ ƒ ˆ Š Ž ˆ αƒ ƒ ƒ Š ƒ ˆ Ž d

4 ƒ Š Ž Ž ƒ ƒ Ž Ž ƒ Š ŽŽ Š Ž Šƒ ƒ ƒ Š Š Š Ž Ž ˆ Š ˆ Š ƒ Š Ž š Šƒ Ž ˆ ˆˆ ƒ ˆ Š Š ƒžž ƒ ƒ Š Š ƒ ƒ ˆ ƒ ƒ ˆƒ ˆ ˆˆ Žƒ ˆ Š Š ƒ ƒ Ž Š Š ˆ ˆ ƒ Ž ƒ ƒ ŠƒŽŽ ˆ Š Ž ˆ Ž Žƒ ƒ Š ƒ ƒž ƒ Šƒ ƒ Ž ƒ ƒ Ž Š ƒ Šƒ Ž ƒ Š ƒ Ž ˆˆ ƒ ˆ ƒ ˆƒ ˆ ŽŽƒŽ š Ž ˆˆ Ž ƒ ƒ Š ˆ ˆ Š Šƒ Ž ŠƒŽ ƒ Š ƒ Ž Š ˆ Ž ƒ ˆ Ž ƒ Š Ž ˆ Ž ˆƒ Ž ƒ Š ˆ ƒ ˆ ƒ Š ƒ Šƒ Š ƒ ŽŽ Ž ƒ Šƒ ƒ ˆ Š ƒ ƒ ˆ Š Šƒ ˆƒ Šƒ Ž ƒˆˆ ƒžž ˆ Ž Š š ƒž Šƒ Š ŽŽ ˆ Š Šƒ Šƒ Š ƒ ŽŽ ƒ ŽŽƒ Ž ƒ ƒ ŽŽ ƒš š ƒ Š Š Š š Š Š ƒ Žˆ ƒžƒ Š ƒ ˆŽ ƒ ƒž Š Š ƒ ƒ Š ƒœ Ž Žƒ Š š ƒ Š ƒ Ž œƒ ˆ š ƒ Ž ƒ ƒˆƒ Ž ˆ ƒ ˆƒ Šƒ ƒ ƒ Š ƒ Ž Š ƒ ƒ Š š ƒ Žƒ d

5 Š ƒ ƒ ƒ Ž ƒ Ž ˆ ƒ ƒ ˆ ˆˆ ƒ š Žƒ Ž α ƒ ƒ Ž š β Š ƒ Š ˆˆ α ˆ Š Š αƒ α ƒ Ž ˆˆ Š š ƒ Š ƒ ƒ ˆ Š ƒ ƒ Ž Žƒ Š ˆ ˆ Š Ž Ž š Ž ˆ Š ˆƒ Ž α Š Š ˆ Š ˆƒ Ž Šƒ ƒ ƒ ƒ Žƒ ˆ Š Ž š Ž ˆ ˆ α Ž ƒ ƒž ˆ Žˆ ƒž Š ƒ ŠƒŽŽ ƒž ƒ Žƒ ƒ Š Ž Š ˆˆ ˆ ˆ α ƒ ƒ Š ƒ Š ˆ Š ˆ α ƒž Š š Žƒ ˆ ƒž ƒ ˆ Š ˆƒ Ž Ž Ž α ƒ ƒž ˆ Š ˆ α Ž ƒžƒ ˆ ˆ Šƒ Š ˆ α Ž ƒ ƒ ƒ ƒ ƒ ˆ ˆ αˆ Š Ž ˆ ˆ αˆ ƒ Šƒ Š ƒž ƒ ƒ ƒ ƒ ˆ Š š ƒ Š ƒž Š ƒ ˆ ƒ Šˆƒ Šƒ ƒ ƒž Š ƒ ˆƒ Š Ž Ž ˆ ƒ ƒ Ž Š Š ƒ Ž α ƒ Ž œƒ Š ƒ ˆ Š š ƒ š Ž ƒ ƒ ƒ ˆ Š α ƒ Š ƒ Š Ž Š Ž ˆ Ž Ž Ž Žƒ ƒ š ƒ Ž ˆ Š Ž Ž ƒ ƒžžˆ ƒ ˆ Š ƒ ƒ ƒ Š š ˆ š Ž ƒ Ž ƒ ˆ ˆ Š Š d

6 ƒ ƒ Š Šƒ ˆ ƒ ƒ Š ƒ ƒ ˆ ƒ Ž ƒ Š Ž ˆ α Ž ƒ Ž Šƒ ˆˆ ƒ Š ƒ Ž Š Š Šƒ αšƒ ƒ ƒ Ž Ž ˆ ƒ ƒ Žˆ ƒž ˆŽ ŽŽ α ˆ Žˆ ƒž ƒ Ž ˆ Š Ž Ž ƒ Žƒ ƒ Šƒ ƒ ˆ Š ˆ α Š ƒ Š Š Š Žƒ ˆ Š Ž š Š Š α ˆ ƒžž ˆ ƒ Ž ƒ ƒ Ž Žƒ ƒ Š ƒˆˆ ƒž ƒ ŽŽ Ž Š Š ˆ α Š ƒ ƒ ƒ ƒ ˆ Š ˆˆ š ƒžž ŽŽ ˆ Ž Ž Šƒ ƒ ƒž Ž ƒ α ƒ ƒ Š Žƒ α ƒ ƒ ƒ ƒ Š Š ƒžž š ˆ ˆ α ƒž ˆ ŽŽ Ž ƒˆ ƒˆ Ž ˆˆ Žƒ ƒ ƒ Š Š α ƒ ƒžž ƒ Šƒ Žˆ ƒž ˆ ƒˆ ˆ α Ž ŽŽ Ž Š ƒ ƒ Ž ƒ ƒ ƒ α ƒ ƒ ƒž ƒ Š ƒ ƒ ƒ ƒž Š ƒ ƒ ˆ d

7 ƒ ƒž ƒ Š ƒ ˆ αˆž ˆŽ Š Š ˆ Ž š ƒ ƒž ˆ αˆž ˆŽ š ƒ Ž ˆ Ž ƒ ŽŽ Ž Š ƒž ƒž ƒ ˆŽ ƒ Š ƒ ˆ ƒ ƒ ŽŽ Œ Žƒ ƒ ƒ Ž Ž ƒ ƒ Ž Š ˆ ƒ Š ƒ ƒž ŽŽ ƒ Š ƒ Ž ƒ ƒ ƒ Ž ˆ Š ƒ ƒ š Ž ƒ Ž Ž ŽŽ ƒ ˆ ƒ ˆ ŽŽ ƒ ƒž ƒ ƒ ƒ ƒ ƒ Š Š ƒž Žƒ ƒž ƒ Š ˆ ŽŽ ƒž ˆ ƒ ƒ ƒ š š ƒ Š Ž ƒžš š ƒ ƒ ˆ Š ƒ Ž ƒž Š ƒž ƒ ƒ ƒ ƒ ƒ ˆ ˆ ƒ Š Š š ŽŽ Žƒ Žƒ ƒ ƒ ˆ ƒ ƒ ƒ Šƒ ƒˆ Š ƒž ƒ ƒ ƒ Ž e

8 ƒž ƒ ŽŽ ˆ ˆ ƒ ƒ Š ˆ Ž Šƒ ˆ ƒž ƒ ƒ Žƒ ƒ š ŽŽ Žƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ Ž ŽŽ Ž ƒ ŽŽ Š Ž Ž Š Š Šƒ ˆ Š ˆ ƒ ˆ Š ˆ ŽŽ ƒ Š ƒ Š ŽŽ ƒ Žƒ Š ˆ Š ƒ ƒˆ Šƒ ƒ Žƒ ƒ ƒ ˆ Ž Ž ŠƒŽŽ ƒ ƒ Š Š ƒ Žƒ ƒ š ŽŽ ƒ Ž Œ Š ƒ Ž ˆ ƒ ƒ š ˆ ŠŽ Žƒ ƒž ŽŽ ˆ š Š ƒ Ž ƒ Ž ƒ ƒž œ Š ƒž Ž ƒ ƒž Ž ˆ ˆ α ƒ ƒ ƒž Œ ˆ μ ˆ ƒ ƒž ƒ ƒ ƒˆ ƒ Žƒ ƒ ˆ α Ž ƒ ˆ ƒ ƒž ˆ Ž Žƒ ƒž Š Ž ŽŽ ƒ ŽŽ š ƒ ƒ Žƒ ƒ ƒž š Ž ƒ ŽŽ Œ Ž ŠƒŽŽ ƒ ƒ ƒ Š š ŽŽ e

9 ƒ ƒž ƒˆ ƒ š ƒ ˆ ƒ ŽŽ ˆŽ ƒ ƒž ˆ ƒ Ž ŽŽ ƒ Ž Ž Š ƒ ŠŽ ŽŽ Š Ž ƒ ƒ ƒ š Ž ƒ ŽŽ Š ƒ Ž ƒ ƒ ƒž Š ˆ ŽŽ ƒ ƒ ƒ Ž ˆ ƒ ƒ Ž ˆ ƒ ƒ Žƒ ŽŽ Žƒ Š Ž ŽŽ Ž Ž Š Š Ž ŽŽ Š Ž Ž ƒ Ž ƒ ƒˆ ƒ ˆ Ž Ž Ž ˆ μ ˆ š Ž ƒ ƒ ƒžƒ ƒž ŽŽ ƒ ƒƒ š ƒ Š ƒ ˆˆ ƒ ƒ ˆˆ ƒ ˆˆ ƒ ƒ ˆ ŽŽ ƒ ˆ Ž Ž ƒ ƒ ƒž ƒ ƒž ˆ ƒž ƒ ˆ ƒ Ž šž ƒ ŽŽƒ ƒž ˆ Š ˆ ƒ ƒ Šƒ ˆ ƒ e

10 Ž α ƒžˆ ƒ ˆ ƒ Ž ƒ Ž ˆ ƒ ƒ ƒ Ž Ž ƒ Š Š ƒ ƒ ˆ Š Šƒ Š ƒ ƒ ƒ Žƒ ƒ Ž Š Š ƒ ƒ α ƒž Š ƒ ƒ ŽŽ ŽŽ ˆ ˆ αˆž ˆŽ š ˆ αˆž ˆŽ ƒ Š ƒ ƒž š ƒ ƒ ƒ Žƒ ˆ Š ƒ ˆ α Δ/Δ ƒ Ž Ž Š Ž ˆ ˆ α ˆ ƒˆ ƒ Žƒ ƒ ƒ ˆ Ž ˆˆ Ž Ž ˆ ŽŽ Ž ƒž Šƒ Š š Ž Ž ƒ ˆ ƒ ƒ Ž ˆ Š ˆŽ š Š ƒ ˆ α1 Š Š ƒž ƒ ƒ Žƒ ƒ Ž Šƒ Š ƒ Ž ˆ ƒ ƒ Š š ƒ ƒ Š Š Š ˆƒ Š Š Šƒ Š Ž ƒ ƒ ƒ Šƒ ƒ Š ƒ Šƒ Š ŽŽ Š ˆˆ ˆ α ˆ Š Œ ƒ Ž ƒ ƒž ƒ ˆ ƒžž Š ƒ ˆ Š ƒ ŽŽ ƒ Žƒ Ž Š ƒ ˆ ƒˆ ƒ Žƒ ƒ ƒˆ Š Š Š ƒ ˆ ˆ ƒ ƒž ƒ ˆ Š ƒ ƒ Žƒ ˆ α Δ/Δ ƒ Ž ƒ ƒž Š ƒ ˆ ŽŽ ƒ Š Š ˆ α Δ/Δ ƒ Žƒ ƒ ƒ Ž e

11 Š Š ƒ ƒ ƒ ƒ Ž Š ƒ Ž ŽŽ ƒ ƒ Š Š ˆƒ Šƒ ƒ Ž ƒ Ž ƒ ƒ ƒ Ž ƒ Ž ŽŽ ˆ ƒ ƒ ƒž ƒ ƒž œ ˆŽ ˆ Ž ƒ ƒ ƒ š ˆƒ Ž ƒ ƒžž ˆ ƒ ˆˆ Š ƒž Š Š Š ƒ ƒ ƒ Ž ˆ ƒ ŽŽ ƒ ƒ Š Š ˆ ƒ ˆ ŽŽ ƒ ƒ ƒž ˆ Š ˆ α Δ/Δ ƒ ƒ ƒ Š Š ƒ ƒ Š Ž ˆ ŽŽ ˆˆ Š Š Š Š ˆ ƒ ƒˆˆ Š ƒ ˆ ˆ α, ˆ ƒ ƒ ˆˆ Š ƒ š ƒ Š ƒ Ž ˆ ŽŽ ƒ Š ŽŽ Š š ˆ α Ž ƒ ƒ ƒ Š Š ƒ Š Š ŽŽ Š ˆˆ ˆ α ƒ š ƒ ƒ ƒ Š ƒƒ ƒ Žƒ ƒ Šƒ ˆ ˆ α Ž Žƒ ƒ ƒ Ž ƒ ƒ ƒ ˆ ƒ Š Ž ƒ Ž ƒ ƒ ˆ Š ŽŽ ˆ ƒ ˆ Ž Ž ƒ ˆ Š ˆ ˆ α Ž Š Š ˆ α Δ/Δ ƒ ˆ α +/+ ) ˆ Š ƒ ƒ Šƒ ˆ Š Šƒ ƒ ƒ ƒ ƒ Š ƒ Š ƒ ƒ ˆ Šƒ ˆ α ƒ ˆŽ ƒ ƒ ƒ Š Š ƒ ƒ Ž Šƒ Š ƒ ˆ dd

12 ˆ α ƒ Ž ƒ ƒˆˆ Š ƒ ˆ Š ƒ Š Ž ˆ ˆ α ƒˆˆ Žˆ ƒž ˆ ƒ š ƒ ƒ Ž ˆ ƒ Š ˆ ˆ ˆ Š Žˆ ƒž ˆ Ž ƒ Ž Šƒ ƒ Ž Š ƒ ƒ Žƒ ƒ Š ˆ Š Š ˆ α Šƒ ƒ Ž Žˆ ƒž ƒ ƒ ˆ ˆ ƒ ƒ Žƒ ƒ Š ŽŽ ˆ ƒ Ž ƒ ƒ Žƒ ƒž ˆ ŽŽ ˆ Š ƒˆ ƒ Žƒ ƒ ˆ α Δ/Δ ƒ Žƒ ƒ ƒž Žƒ ˆ ƒ Š Ž Ž ƒ ƒž ƒ ƒ Š ƒž Š ƒž ƒ ƒ ƒ ˆ ƒ Š Žƒ ˆ ˆ α Δ/Δ ƒ Ž ƒ ƒž ˆ ƒ ƒ ƒ ƒ ƒ Š Š ƒ ˆ ŽŽ ƒ Š ˆ Š ƒž ƒ Žƒ Š ƒ ƒž ƒ ƒ ˆ ƒˆ ƒ Žƒ ƒ Š ƒ ˆ ƒ ƒ ƒž œ ƒ ƒ ƒžž ˆ ƒ ƒ Ž ƒ Ž œ ˆ α Δ/Δ ƒ ƒ ƒ ƒ ƒ ˆ Š ƒ Š ƒ ƒ ƒ ƒ Š Š ƒ ˆ ƒ ŽŽ Ž ƒ ŽŽ ƒ Š Š ƒ ƒ Šƒ Ž ˆ α ƒ ƒ Ž ƒ Š ˆ Š ƒ ƒ Š Šƒ ƒ Ž ƒ Š Žˆ ƒž Š ƒ Ž ƒ Ž dd

13 α ƒ ˆŽ Š ƒ ˆ Ž ƒ š ƒ Ž ŠƒŽˆ ˆ ƒžž ƒ Š ƒ ƒ ƒ ˆ š ƒ ƒ ˆƒ ƒ ƒž Ž ˆ α 14 Š ˆ ƒ ƒ Š Š Šƒ ƒ ˆ ƒ ˆŽ Š ƒ ˆ ˆ α Žƒ Š ƒ Ž ƒ ŽŽ ˆ ˆ αˆž ˆŽ š ˆ αˆž ˆŽ Š š š š ˆ š ƒ ˆˆ ƒ ˆ ƒ Žƒ ƒ ˆ Ž ŽŽ ƒ Žƒ Ž ƒžž ˆˆ ƒž ƒ Š š ƒž ƒ ƒ Š Š ƒˆ ƒ Žƒ ƒ ˆ α Δ/Δ ƒ Š Žƒ Ž Ž ƒ ƒ ˆ Ž ŽŽ ƒ š ƒ ƒž ƒ ˆ ƒ ˆ ƒˆ ƒ Žƒ ƒ ƒ ƒ Ž ŽŽ ƒ ƒž œ ˆ α Ž ƒˆˆ Š Ž ˆ Š ƒ Š Ž ƒ ƒ ƒž ˆ ƒžƒ Ž ŽŽ ƒ Ž ˆ ˆ Š Š ˆˆ Ž Ž œ ƒ ƒ ƒ Š ƒ ˆˆ Š ˆ ˆ Š Š Š ˆ α Š Ž Žˆ ƒžƒ ˆ Š ƒ ˆ ƒ ƒ Žƒ ƒ Š š ˆƒ Ž ƒž dd

14 ˆˆ ƒžž ƒž ˆ α Δ/Δ ƒ Ž Š Š ˆ Š ƒ Š ˆˆ α ƒ ƒ Žƒ Š ƒ Ž ŽŽ Š Š ƒž Ž ƒ Ž Š Ž ƒ ˆ ˆˆ ƒž ƒ Ž ŽŽ Š ƒ Š Š Ž ƒ Šƒ Š ƒ ˆ α ƒ ƒžž ƒ š Ž ƒ Ž Š Š Š Šƒ ƒž Ž Š α ƒ Š ƒ ˆ ƒ ƒ Ž œ α ƒ ˆŽ Š ƒ Ž ƒ Ž Š Ž ƒ Š ˆ Šƒ ˆ ŽŠ ƒ ƒ ˆ Ž ƒ ƒ ƒ Ž ƒž š ˆ Š ˆ ƒ ƒ ˆŽ ƒ Š ˆƒ Šƒ Ž ƒž ˆ αž ƒ Š Š œ Šƒ ˆ α Š Ž ƒ Ž œ ˆ ƒ Š Š ˆ ƒ ƒ ˆ α, ŽŽ ˆ Š š Ž Ž š ˆ ƒž ƒž ƒ ƒ ƒ Š ŠƒŽ ƒžš š ƒ ƒ Ž œƒ ˆ Š α Ž Š ƒ ƒ ƒ ˆ ƒ Š ˆ š Ž Ž ƒ ƒ ƒ ƒ ˆŽ š š ƒ Š š š Ž ƒž ƒ ƒ ˆˆ ˆ Š ˆ α ƒ Ž œƒ dd

15 Š Š α ƒ Ž œƒ ƒ ˆ ˆ ƒ Žƒ ƒ š Š Žƒ Ž ƒ ƒ š Š Žƒ ˆ Ž ƒ Š ƒ ƒž ƒ ˆ ƒ Ž ˆˆ Š ˆ α Δ/Δ ƒ Ž ƒž ˆ ƒ Ž ŽŽ ƒ ƒ Žƒ Ž ˆ Š Ž ƒ Š Ž ˆ Š ˆ α ƒž ˆ Š ƒ ƒ ƒ Žƒ ƒ Š Š Š ˆ ƒ ƒž ˆ ƒ ˆˆ Ž ƒ ƒ ƒ Š ˆ α ƒ Š Ž ˆ α Žˆ ƒž ˆ ƒ Žƒ ƒž ˆ ŽŽ ƒ ƒž Š ƒ Ž Š ƒ Ž ƒ ˆ ƒ ƒž ƒ Žƒ Š ˆ α Δ/Δ ŽŽ ƒž ƒ Š ƒž Š ƒ Ž ƒž ˆ Š ƒ Žƒ ƒ Š ƒ Žƒ Š ˆ Š ƒ Ž Ž ƒ Š Ž ƒ ƒ ƒž ƒž ƒ Š ƒ ƒ Š Ž ˆ α Δ/Δ Š Ž ƒ ˆˆ Š ˆ ˆ α Δ/Δ ŽŽ Ž ƒ Š Ž Š Šƒ Šƒ ƒ ˆ Ž Šƒ ƒž Ž ƒ α š ƒ α ƒ ƒ ƒ ƒž Žƒ ˆ Žˆ ƒž Š Š Š ƒ Ž œ αƒ ˆ Š Ž ˆ αž ƒ ƒ ƒ š ˆ α ƒ ƒž œ Š Ž Ž ˆ Š ŽŽ ˆ ƒ ˆ Š Š ˆˆ Ž ƒ Ž Ž ƒž dd

16 ƒ ˆ ƒ ƒ š ˆ αƒˆ Ž ˆ α Ž Š ƒ Ž Š Ž ƒ Ž Ž ˆ α Ž ƒ ƒ ƒ Žƒ ˆ α ƒ Ž ƒ ƒž Š ˆ ˆ α Δ/Δ ƒ ŽŽ ŽŽ αšƒ Žƒ ƒ ƒ Š ˆ Š Š ˆ ƒ Šƒ ƒ ƒ š ƒ ƒ ƒ α Š ˆ ƒ š Ž Ž Š ˆ š ƒ ƒ Ž Ž ƒ Ž Š š ŽŽ ƒ Š Š Š ƒ ˆ α Š Š Ž ƒ Ž ƒˆˆ Š ƒ Ž ˆ ƒ ˆ Š ŽŽ Ž ˆ Ž ƒ ƒ Ž ƒ Š ˆ ŽŽ Š Š ˆˆ Šƒ ˆ Š ŽŽ Ž ƒ ƒž Š ˆ α Δ/Δ ƒ Ž Š ˆƒ ˆ Š ƒ Š ˆ α Δ/Δ Š Ž ˆ ƒ ˆ ƒ ˆ Ž ŽŽ Šƒ ƒ Ž ˆ ˆ α Δ/Δ Š Š ƒ Šƒ α Ž ƒ ƒ ƒ ƒ ŽŽ Ž Žƒ ƒ Ž ƒ ƒ ˆ Š ƒ ˆ Ž ƒ ƒž ƒ ŽŽ ƒ Žƒ ŽŽ Ž ˆ Ž Š ƒ ƒ Žƒ ˆ Š ƒ Ž ˆ Š α ƒ ˆ Š ŽŽ ƒžž Šƒ Š Ž Šƒ Š ˆˆ Ž Š ƒ Ž ŽŽ Š Ž Ž ƒž dd

17 š ƒ š Ž Š Š Š ˆˆ ˆ ˆ α Δ/Δ ƒ ˆŽ Š ƒ Ž ƒ ƒ Ž Ž ˆƒ ƒ Š ƒž ƒ Š ƒ ƒž œ ŽŽ ˆ ƒƒ ƒ ƒ Š Ž Žƒ ƒ ˆ Š Ž ƒ š ŽŽ ƒ Š Š ˆ ŽŽ ƒ Š ˆ α Δ/Δ ŽŽ ƒ Ž ƒž Š Ž ƒ ƒš Š ˆ Š ŽŽ ƒš Š ƒ Žƒ ˆ ƒ ƒ ˆƒ Ž ƒ ƒž ˆ Š ƒž ƒ ƒ Š ƒž ƒž Š ˆ α Δ/Δ ŽŽ ˆ Š Š ˆˆ Ž ƒ Ž ƒž Ž ˆ Š ƒ Ž Š ˆ ƒ ˆˆ Š ƒ Š ƒ Ž ƒ Šƒ ƒƒ ƒ ƒ Š Š ƒžƒ ˆ Š ŽŽ ƒ ˆ α Ž ƒž ƒ Ž Š ƒ Ž ƒ ƒž ˆ Š ƒ Ž ƒž ƒ Žƒ Š Ž ˆ Š α ƒ de

18 Ž Žƒ Šƒ ˆ Žˆ ƒž ƒž ƒ ƒž ƒ ƒ Žƒ Ž Ž š ƒƒ Š š ƒ ƒž Š Š Š ƒ ˆƒ α,šƒ Ž Ž ƒ Š ƒž ƒ ŽŽ Š Šƒ ƒž ƒ Ž ˆ α ƒ ƒ ƒž Š Š ˆ Š ƒ Š ƒ ƒ Š ƒ ˆ Š ƒ Žƒ ƒ ƒž ƒ Š ƒ Šƒ Ž Šƒ Š ƒ ŽŽ Š α ƒ α Š Šƒ ƒ Š ƒ Š Ž α ˆ ˆ ŽŽ ƒ Žƒ ƒ ŽŽ ƒž ƒ ˆ Š ƒ Ž ƒ ƒ Ž ƒ Š Š Š ˆ ƒž Ž α Š ƒž ƒ ˆ ƒ Š ƒ Žƒ ƒ Ž ƒžž Š ƒ Š ƒ ƒ α ƒ ˆ Š ˆˆ ƒ ˆˆ Šƒ Š Ž ƒ ˆ š Š ƒ ˆ Šƒ ƒ Šƒ Š ˆ ƒ Ž œ α Ž Š ƒ ŽŽ α ˆ Ž ˆ ƒ. ˆˆ Ž ƒ Žƒ ƒ ƒ Žƒ ƒ ƒ ƒ Ž ˆ α Š Žˆ ƒž ˆ Š ƒ ƒ ƒ Ž ˆ α Š Š ƒ Ž ƒž ƒž ƒ de

19 Š ƒ ˆ Ž Šƒ Šƒ ˆ α ƒ ƒ ƒ ƒ Ž ƒ ƒž ŽŽ ƒ ƒ Š Ž ˆ ˆ Ž ƒ ƒ ƒ Žƒ ˆ α α Ž ƒ Ž Š Žƒ ƒ ˆ Š Š ƒš š ƒ ƒž Šƒ ƒ ƒ ˆ ƒ ƒž ˆˆ ƒ ˆ Š ƒ Ž œƒ ˆ ƒ Š ƒ Š š Ž ƒ Š ƒ ƒ ˆ ƒž Š ˆ ƒ ƒ ƒ ƒ Š Š Ž Ž ˆ Ž ƒ ƒ Š š Š Š Ž ƒ š Ž Ž Žƒ Š ƒ Š Ž Šƒ Ž ƒž ƒ ƒ Ž ƒ ƒ ƒ ˆ ƒ ŽŽ ƒ Š š ƒž š ƒ Š Ž ƒžž Š š ƒ ƒ Š Š Š Š ƒšƒžž ƒ ˆŽ ƒ Š Š ˆ ˆ Š α ˆ ƒ ƒ Ž ˆ ˆ αƒ ƒ ƒž Š ƒ Ž ƒž ƒ Š Š Š Š ƒ ˆˆ Š ˆ α Š ˆ Š, š ˆˆ Ž Šƒ Š Ž ƒ α ƒ ƒ Šƒ Š š ƒž ƒ ˆ ŽŽ ƒ ˆ ƒ Žƒ ƒ Š ˆ Š Ž Š ƒ ƒ Ž ƒž ƒ Ž Šƒ Ž ˆ Š Š Ž ƒ α Š ƒ Ž ƒ ƒ ƒ Žˆ ƒž de

20 ƒ Š ˆ Šƒ Ž ˆ α Ž ƒ Ž ˆ ƒ ˆ Š Ž Š Ž Ž ƒ ƒ Ž Š ˆƒ Ž ˆ ƒ Š Š α Š ƒž ƒ Šƒ α ƒ ƒ Š Š Š Š ƒ ˆˆ ˆ α Ž ƒ ƒ ˆˆ ˆ š αšƒ ƒ Ž Ž ˆ Š ƒ š ˆ α Š ƒ Ž Š Š Ž Šƒ ƒž Š ƒ ƒ ˆ Š ƒ ˆ Ž ƒ Ž Š ƒ Žƒ ˆ Š α α ƒ ˆˆ ƒ Ž ƒˆˆ ƒˆ ˆŠ ƒ ŽŽ ƒ ƒ ŠƒŽŽ Š Ž ˆ α ƒ ƒ ƒ ƒ Žˆ ƒž ƒ Ž Š ƒ ƒ ƒž ˆ Ž ˆ Žˆ ƒž Š ˆ α Δ/Δ ŽŽ Š Š Žƒ Š Š ƒˆ ƒ ƒ Žƒ ƒ ƒ ˆˆ Ž ƒ ˆ α +/+ ŽŽ ƒ ƒ ˆƒ Ž ƒ Ž Š ƒ Ž Ž ƒž ˆƒ Ž ƒ Ž ˆ Šƒ Š Š š ˆ Š Ž ƒ Š Ž ˆ α ƒ Žƒ Š ƒ Žˆ ƒž Š ƒ ƒœ ˆˆ Š ƒ ƒ ƒ ƒˆ ƒ ƒžž ˆˆ Ž ˆ α Ž ƒ Šƒ Šƒ ƒ Š Ž ˆ α Ž ƒ ƒ ƒ ƒ Žƒ Š Ž Š Š Š Š ƒ ƒ Ž ƒ Šƒ α ƒ ƒž ƒ ƒ ƒ Ž Ž ˆ ƒ Š Š Š ƒ Žƒ ƒž ƒ Šƒ ƒ Š ƒž ƒ Ž Š ˆ Šƒ Ž ƒ ˆ Š ƒ ƒ ƒ α ƒ de

21 ƒ ƒž Š Š ˆ Š ƒ Š Š α ƒ ƒ ƒ Š ƒ ƒ ˆˆ Ž Žƒ Ž ˆ ˆ Ž Šƒ ƒ ƒ ƒ ± ±ƒž ƒ ƒ ƒ ˆ Ž Š šƒ ƒ ƒ Š ˆ Š Š ƒ Œ ƒ ˆ ƒ ˆ ƒ ƒ ˆ ƒ Š Š ƒ ƒ ± ƒ ƒ ƒ ƒ ˆ ƒ ƒ ˆ Š Š Š ƒ Š ˆ š ƒ ƒž œ ƒ ƒ ƒ ˆ ƒ Š ƒ ƒ ˆ š ƒ Ž ƒ ƒ ƒž œ ƒ ƒƒ ƒ ƒ ƒ Š Œ Š ƒ Šƒ Š ƒ ŽŽƒ Š ƒ ƒ ƒ Š ˆ ƒž ƒ ˆŽ ˆ Ž Š ƒ Š Žƒ ˆ ƒ ƒž Ú ƒ ƒ ƒ ˆ Ž Žƒ ƒ Š ƒ ŽŽ ÚŽ ƒ ƒ ƒ Ž Œ ƒ ƒ Ž dd

22 ˆ d ' E :D dddd dee dd ddde dded d E ^< :,D : ^ dddd ee e dded ddee d / & z ^ ^ z D> E ddde dd dd dddd dddd d ^ '>, dddd dde d dee dde d ^ '> t '> D deed dd dd ddde dddd e < : Z^ ^ D,/&d,/&d E Z dddd dd d e dd e D z < t t: d, W > / W^ /W^ d : dddd dee de ddddd dddde e d < ' E z t Z,/& d ^ dddd e d ded ddd e ' s ^, d dddd ddd dd dedd dedd dd E W ' t Y E dddd dd d ddd ddd dd < < & E < E < < d s'&,/& d dddd ddd dd ddde dded dd W D > d ^ :, D > W ^ Z > ^,/& d Z ddde dee d ee ddd dd, d ^ ^ Z Z, D d DK: dddd dd d ddd dde dd ^ d < & : d ^ dddd e d ded ded dd K ^ : : D D/^d,Kye > Z dddd dd dd ede edd de <,, Z< ^,:,,Ky,Ky D>> > deee dd d eee eee de >,: Z ^ &,Kye D/^d > deee dd dd deed deee dd

23 de < s ^ D>> E Z ddde e dd edd edd de, >, y,^ > ^,/&d dddd dde dd dded dede dd t z > z D ^E W z > d,/&d ^ dddd e d dee ddd dd Z W < > K > & <,/& d ^ dddd dd d dde ded dd t W / D ^ d ^ t D> D d D>> ' ddde dd dd deed deed dd z D < W >& e dd E D ddde dd e edd ede dd Z, W D D E t, d Z dddd ed dd dddd dddd dd < Z ^ & D Z < / ^ deed dee ddde ddde ddde de, < W < t : Z ' ddde dd d dd de de D : z > z Dt Z,/& d dddd d d dde ddd de E > h ' W / ^ deee ded ddde ded dee de < Z /,,, > t : E Z dddd dd dd ed dd D > K E & d /d > dddd de e dede dedd dd > : ^ ' d E dddd ddd eede ddd ded dd < < : d h ^ D ^ ', e D d W d DK: deee de dd dedd dedd dd E,,/&d E Z ddde e e edd edd dd D D s W ^ tz ' : ^ Z > d d dddd ddd dd deee deed dd d : : ',/& d dddd e d ddd ddd dd

24 de D :, DD W <,/& d < W E ^ h^ dddd dde dd ddded dddee de < < < tz > D < t' : /,/&d s,> W> ^ dddd d d ed de D :< s :Z Z : :^ > td < Z d s,>,/&d s,> dddd d d dde ddd dd

25 Ž α ˆ Š ƒ ˆ ƒ Ž ƒ ƒ Žƒ ƒž ˆ ƒ Žƒ Š ƒ š ŽŽ Ž ˆ α Δ/Δ ƒ ˆ αˆž ˆŽ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ ƒ ˆ ƒ ŽŽ ƒ ƒˆ ƒ Žƒ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ˆ Ž ŽŽ ƒ ƒ ƒ ƒˆ ƒ Žƒ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ Ž ˆ ŽŽ ˆ ƒ Š Šƒ Š ŽŽ ƒ ƒžž Ž Š ƒž ƒ Žƒ Š ˆˆ ƒ Žƒ ƒ ƒ Š Š ˆ ŽŽ ƒ ˆ ŽŽ ˆ ŽŽ ƒ ƒ ˆ Ž ŽŽ ƒž ˆ ˆˆ ƒ ƒ ˆ ƒ ˆ ƒ ƒ ƒ ƒ ƒ ˆ Š ƒ Ž ŽŽ ŽŽ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ ŽŽ ˆ Ž Š Žƒ Š Ž ˆ Š ƒ Žƒ Š ƒž ƒ μ ƒ ƒ ˆ ŽŽ ˆ Š ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ˆ Ž ˆ ŽŽ ˆ ƒ Š ƒ ƒ Žƒ ƒ Ž ƒ Ž ƒ ƒ š ƒ ƒš ƒž Ž Š ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ dd

26 ˆ α Ž ƒ Ž ƒ Š ƒ ƒž ƒ Š ƒ ƒ Žƒ ƒž ˆ ƒ ˆ š ƒ Žƒ Š ŽŽ ˆ Ž ˆ Š ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ Š Ž ˆ Š ƒ ƒ ƒ Š ƒ ˆ ƒ ŽŽ Ž ŽŽ ƒ ƒ ƒ ŽŽ ƒ ƒˆ ƒ Žƒ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ Ž ƒˆ ƒ Žƒ ƒ ƒ ˆ ƒ ƒ ƒ ƒž œ ƒ ƒž ƒ ƒ ƒž Ž ƒ Ž Š ƒ ƒ ŽŽ ƒ Ž ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ ƒ ƒ ƒž ˆ ƒ ƒž Š ˆˆ ƒ Ž ˆ Ž ŽŽ ˆ ƒ Š Šƒ Š ŽŽ ƒ ƒžž Ž Š ƒž ƒ Žƒ Š ˆˆ ƒ Žƒ ƒ ƒ Š Š ˆ ŽŽ ƒ ˆ ŽŽ ˆ ŽŽ ƒ ƒ ˆ Ž ŽŽ Ž ƒ Ž Š ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ ˆ α Ž ƒ Ž ƒ ƒ Ž Ž ˆ ƒ Žƒ ƒž ˆ ƒ Žƒ Š š š ŽŽ ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ ƒ ˆ Ž ŽŽ ˆ ƒ Žƒ ƒ ƒž ƒ ˆˆ ƒˆ dd

27 ƒ Žƒ ƒ ˆ α Δ/Δ ˆ αˆž ˆŽ ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ ƒ ƒž ˆ ƒ ƒ Ž ˆ ŽŽ ƒ ƒˆ ƒ Žƒ ƒ Š ƒ Š Ž Žƒ ˆ ˆ α Δ/Δ ƒ Ž Š ˆˆ ƒ Žƒ ƒ ƒ Š Š ˆ ŽŽ ƒ ˆ ŽŽ ˆ ŽŽ ƒ ƒ ˆ Ž ŽŽ ƒ ƒ ˆ ƒ ƒ ƒ ƒ ƒ ˆ ƒ ƒ ƒž ƒ ƒ ƒ ƒž œ ƒ ˆ Ž ŽŽ ƒ Ž ƒ Ž ƒ Ž Š ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ ˆ ŽŽ ˆ Š Ž ƒ Ž ƒ Ž Š ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ Š ˆˆ Žˆ ƒž Š α. ƒ Žƒ ƒž ˆ ƒ Žƒ Š š š ŽŽ ˆ ƒ ŽŽ ˆ ˆˆ ƒ Žƒ š ŽŽ ƒ ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ ƒ ƒž ˆ š ƒ ˆ ƒ ƒˆ ƒ Žƒ ƒ ƒ ƒ ˆ Ž ŽŽ ƒ Ž ƒ Ž ƒ Ž Š ƒ ƒž œ ˆ ƒž ƒ Š ƒ ˆ Š ƒ Ž ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ de

28 Ž ƒ ƒ ˆ α ƒ ƒž Š Š ƒž Ž ƒ. š ˆ ƒ Ž ˆ š Ž Ž ŽŽ ƒ Š ƒ Š š ŽŽ ˆ Š Ž Š Ž ŽŽ Ž ˆ š š Š š š ƒ š Ž š ƒ š ƒ ƒž œ ˆŽ ƒ Žƒ ƒž ˆ ƒ Žƒ Š š ŽŽ ˆ α Δ/Δ ˆ αˆž ˆŽ ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ Š Ž ˆ Š ƒ ƒ ƒ Š ƒ ˆ ƒ ŽŽ ƒ Ž ŽŽ ƒ ƒ ƒ ƒˆ ƒ Žƒ ƒ ƒˆ ƒ Žƒ ƒ ƒ ˆ ƒ ƒ ˆ ƒ Š Š ˆ Š ƒ ƒ ƒž œ ƒ ƒž ƒ ƒ ŽŽ ƒ Ž ŽŽ ƒ ƒ ƒ Ž ƒ Ž ƒ Ž Š Ž ƒ Ž ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ α ƒ ƒˆˆ Š Žˆ ƒž ˆ ƒž Š š ƒ ŽŽƒ Ž ƒ ˆ ˆ Ž ƒ Ž ŽŽ ƒ Žƒ ƒž ˆ ƒ ƒ Žƒ Š ŽŽ ˆ Ž ˆ Š ƒ ƒ Ž š ƒ ƒ ƒ ƒž ˆ ƒ ƒž Š ˆ šƒ ƒ ƒ Š ƒˆ ƒ Žƒ ƒ Š Ž ˆ Š ƒ ƒ ƒ ƒˆ ƒ Žƒ ƒ ƒ ƒž ˆ š de

29 ˆ ƒ ˆ ƒ ŽŽ ƒ Ž ŽŽ ƒ ƒ ˆ ƒ ƒ ˆ ƒ ƒ ˆ Š ƒ ƒ ƒž œ Ž ƒ Ž Š ƒ šƒ ƒ ˆ Š Ž ŽŽ ƒ Ž ŽŽ ƒ ƒ ƒ Ž Ž ƒ ƒ š ƒ ƒš ƒž ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ α ƒ ƒžž ˆŽ ŽŽ Ž ƒ Ž ˆ Ž ŽŽ Ž ƒ ƒ ŽŽ Ž ƒ ƒž ˆ Š Ž ŽŽ Ž Š Ž ˆ Š ˆˆ ƒ ƒ ˆ ƒ ˆ š ƒ š ƒ ƒž ˆ Š Ž ŽŽ Ž Š Ž ˆ Š ˆˆ ƒ ƒ ˆ ƒ š ƒž ˆ Š ƒžƒ Š ƒžƒ ƒž ƒ ˆŽ ˆ ƒ ƒ ƒ ŽŽ ƒ Ž ŽŽ ŽŽ ƒƒ Ž ƒ Ž ŽŽ Ž ˆ ƒ ƒ ƒ Ž ƒ ƒž œ Š ƒ Ž ƒž Ž ƒ ƒ Ž ƒ ƒ ƒ ƒž ˆ ƒ de

30 B2 CD3 B2 CD3 A B C Survival (%) 1 + AE9a Hif-1 + AE9a + MIGR1 Hif-1 + MIGR1 P=.3941 Time (weeks) GFP+ cells in PB (%) weeks weeks * Gr1 + /Mac1 + cells in PB (%) *** * D Hif-1a Hif-1a E F fl/fl D/D GFP (T) 2.74 (B) Gr1 Mac1 B (M) 5K 1K 15K K 25K FSC Gr1 Mac1 B (T) 3.35 (B) (M) K 1K 15K K 25K k.779 Gr1 + /Mac1 + cells in PB (%) G Lin - cells in BM (%) I Colonies / 1, cells P=.2398 P=.9371 P= w 7w Lin - cells in PB (%) H J GFP + colonies (%) 1 1w *** w P=.964 Hif-1 COlonies from mix cells HIF-1 fl/fl P=.5579 fl/fl D/D HIF-1 / Figure 1

31 B2 CD3 B2 CD3 A B C D F Lin - cells in PB (%) Spleen Weight (% of body weight) G Survival (%) GFP + cells (%) *** *** 3 weeks 7 weeks 1 weeks BM Time (weeks) *** ** Spleen ***P= E GFP+ cells in PB (%) WBC (x 1 9 /L) Liver Weight (% of body weight) Lin - cells (%) *** *** 3 weeks 7 weeks 1 weeks 15 *** 1 5 BM *** * ** Spleen H GFP Gr1 + /Mac1 + cells in PB (%) (T) 13. (B) Gr1 Mac1 B FSC Gr1 Mac1 B2 3 weeks 7 weeks 1 weeks Hif-1a fl/fl (M) K 1K 15K K 25K Hif-1a D/D 1.28 (T) (B).851(M) K 1K 15K K 25K Figure 2

32 B2 CD3 A B Survival (%) C 1 Hif Time (weeks) 5 1.1(T) 59.5 (B) Hif-1a fl/fl Gr1 Mac1 B (M) Hif-1a D/D (T) 34.6 (B) (M) D Gr1 + /Mac1 + cells in PB (%) Gr1 + /Mac1 + cells at death (%) 1 1 * 3 weeks 8 weeks 12 weeks PB BM Spleen Hif-1 E 3 P=.251 F 2. P=.5268 WBC (x 1 9 /L) 1 Spleen Weight (% of body weight) G Colonies / 1, cells 15 P= Liver Weight (% of body weight) Hif-1 P=.533 Hif-1 Figure 3

33 A Survival (%) C 1 P= Gr1 + /Mac1 + cells in PB (%) Time (days) Hif-1 B D WBC (x 1 9 /L) Gr1 + /Mac1 + cells (%) WBC-ok ** *** 1 BM Spleen E 2.5 *** 9 P=.772 Spleen Weight (% of body weight) Liver Weight (% of body weight) Figure 4

34 A % of Max 1 C GFP+ cells in PB (%) 1 E WBC (x 1 9 /L) H 15 1 Spleen Weight (% of body weight) GFP weeks 7 weeks 1 weeks F GFP + cells (%) 1 Hypoxia -Dox Normoxia -Dox Hypoxia +Dox Normoxia +Dox Untransduced + Hypoxia Liver Weight (% of body weight) BM B D Survival (%) Gr1 + /Mac1 + cells in PB (%) Spleen 1 P= Time (weeks) 3 weeks 7 weeks 1 weeks G Gr1 + /Mac1 + cells (%) 1 BM Spleen Figure 5

35 A Survival (%) WBC (x 1 9 /L) 1 P= P= Time (days) C D E GFP+ cells in PB (%) B 15 P=.4542 Total weight (g) *** Gr1 + /Mac1 + cells in PB (%) 1 * 9 7 F Spleen Weight (% of body weight) P=.5826 Liver Weight (% of body weight) P=.3376 H Hif-1a fl/fl Hif-1a D/D 1. G GFP + cells (%) 1 BM Spleen Gr1 + /Mac1 + cells (%) 1 * BM Spleen Hif-1 Figure 6

36 A AE9a B BM GFP + cells (%) BM myeloid cells (%) BM GFP + cells (%) Spleen GFP + cells (%) 1 1 HOXA9-MEIS1 *** * Spleen myeloid cells (%) MLL-AF9 Spleen GFP + cells (%) 1 1 * G2/S/M G1 G Annexin V + cells (%) Annexin V + cells (%) HOXA9-MEIS1 BM *** BM MLL-AF9 *** Spleen * Spleen Hif-1 Hif-1 C BM Spleen MitoTracker Normalized MFI (%) 25 *** 15 1 *** Normalized MFI (%) * 1 MitoSOX Normalized MFI (%) 15 1 * Normalized MFI (%) CellROX Normalized MFI (%) Normalized MFI (%) Normalized MFI (%) 15 ** Figure 7 AE9a HoxA9-Meis1 MLL-AF9 AE9a HoxA9-Meis1 MLL-AF9

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