Association of Acute Myeloid Leukemia s Most Immature Phenotype with Risk Groups and Outcomes
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- Felicia Richard
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1 Published Ahead of Print on January 27, 2016, as doi: /haematol Copyright 2016 Ferrata Storti Foundation. Association of Acute Myeloid Leukemia s Most Immature Phenotype with Risk Groups and Outcomes by Jonathan M. Gerber, Joshua F. Zeidner, Sarah Morse, Amanda L. Blackford, Brandy Perkins, Breann Yanagisawa, Hao Zhang, Laura Morsberger, Judith Karp, Yi Ning, Christopher D. Gocke, Gary L. Rosner, B. Douglas Smith, and Richard J. Jones Haematologica 2016 [Epub ahead of print] Citation: Gerber JM, Zeidner JF, Morse S, Blackford AL, Perkins B, Yanagisawa B, Zhang H, Morsberger L, Karp J, Ning Y, Gocke CD, Rosner GL, B. Smith D, and Jones RJ. Association of Acute Myeloid Leukemia s Most Immature Phenotype with Risk Groups and Outcomes. Haematologica. 2016; 101:xxx doi: /haematol Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
2 ƒ ˆ Ž ƒ ƒ Š Š ƒ ƒ Šƒ Š ƒ ƒ ƒš ƒ ƒ Žƒ ˆ ƒ ƒ ƒ ƒ ƒ ƒ ƒ Šƒ ƒ ƒ Šƒ Š Š ƒ Žƒ Š Šƒ ƒž Š Ž Š ƒ ƒ Š Š ƒž ƒ ƒ Šƒ Ž Š ƒ ˆ Šƒ Ž ƒ Ž Ž ƒ ˆ Š Š ƒ Ž Ž ƒ Ž ƒ ŽŽ ƒž Š Š ƒ ƒ ƒž Š ƒ Š ƒ Š ƒ ƒ ƒ Š ƒ ƒž ˆ ƒž Š ƒ ƒ ƒ Šƒ Š Žƒ ƒ ƒ Š Ž Ž ƒ ƒž Š ƒš ƒ Ž ŒŒ ŒŠ ˆŽ ˆ Ž Š Ž Š ƒ ˆ Ž ˆŽ ƒ ƒž ƒ Ž ƒ ƒ Š Š Ž ƒ Šƒ ˆ ƒž Š Š ˆ Š ƒ ƒ ƒ ƒ ƒ Š Š ƒ ƒ Š ˆŽ ˆ Ž Š ƒ ƒ Š Žƒ ˆ ƒ ƒž ƒ ƒ Ž d
3 ƒ Š Š ƒ Ž ˆƒ Ž Ž ƒ ŽŽ ƒ ƒž ƒ ƒ Š Ž ƒ ƒ ˆ ƒˆ ƒ ƒ ˆƒ Ž ƒ ˆ ƒ ˆ ƒ ˆ ƒ ƒ ˆ Ž Ž ŽŽ Š Š ƒ ƒž œ Š Ž ƒž Ž ˆƒ Žƒ ƒ ˆ ƒ Ž ƒ ŽŽ ƒžƒ Š Š Ž Ž Š ƒ ŽŽ Žƒ Š ƒ Ž ˆ Ž ƒ ƒ Ž Ž ƒ ƒ ƒ ƒ ƒž œ ƒ ƒ Ž ƒž ƒ ƒ Šƒ Ž ƒ ŽŽ Š Ž ƒ ŽŽ ˆ Š ƒ Žƒ ƒ ƒž Š Š ƒ š Š Ž ƒž Š ƒ ŽŽ š Š ŠŽ Ž ˆƒŽ Š Š ƒ Š Š ƒ Š Ž ƒ ŽŽ šš Š ŠƒŽ Š Š ƒ ƒ ƒ Šƒ Ž ƒ ƒž ƒ ƒ Ž ƒ Ž ƒ ŽŽ Ž ƒ Ž ƒ Š Ž Š ƒ ƒ ƒ Ž Ž ƒ ƒ Š ƒ Š Ž ƒ ŽŽ ŠŠ ŠƒŽ Š Š ƒ ƒ ƒ ˆ ƒ ˆ ƒ Ž Ž Ž ƒ ƒ ŽŽƒ ˆ ƒ ƒžž ƒž Š Ž Ž ƒ Š ƒ Š Š ƒ š Žƒ Šƒ Ž Ž ƒ ƒ Š Ž ƒž Žƒ Šƒ Š ƒ Š ƒ Ž Š Ž ƒ Š ƒ ƒ ƒ ˆ Ž ƒžž Ž ƒ Ž ƒ ŽŽ Ž ƒž ƒž d
4 Šƒ ƒ ƒ ƒ ƒž Šƒ ƒ Ž Ž ƒ ŽŽ ƒ ƒ Ž ˆ ƒˆ ˆ š ƒ ƒž Š ƒ ŽŽ Š Š ƒžž Ž ƒ ŽŽ ƒ ƒ ƒžž ˆˆ ƒ Šƒ Š Ž ˆ Š Ž ƒ Ž Ž Ž ˆ ƒ ƒž Ž Ž ŽŽ ˆ ƒ ˆƒ Š Š Š ƒ ƒ Šƒ Š ƒ ƒ Ž ˆ ƒˆ ˆ Š ƒžž ƒ Ž ƒ ƒ ˆ ƒ Š ƒ ƒžƒ ƒ Šˆ ˆ ƒ Šƒ Šƒ Ž Ž Š ƒ ƒ ƒ ƒ ƒ ƒ ˆ ƒ ˆ ƒ ˆ ƒ Ž ƒ ŽŽ ŽŽ ƒˆ Š Ž Š ƒ Ž ˆ Š ˆ ƒ ƒ ƒ Ž ƒ ƒ Š ƒ Šƒ Š Ž ƒž Ž ƒ ˆ ƒ ƒ ƒ Ž ˆ Š ƒž ˆ Ž ŽŽ Šƒ ƒˆ Š ƒ ƒž ƒž ƒ ƒ ƒ ƒ Ž Š Ž ƒžž ƒ Ž Š Šƒ Ž ƒ Š ˆ Ž ŽŽ ƒ Š ƒˆ Š ƒ ƒ Š ŠŽ ƒ ƒ Š Ž ƒž Žƒ Š ˆ Šƒ Ž ƒ ŽŽ ˆ Žƒ Š Š ƒ Žƒ Šƒ ƒž Ž ƒž Ž Ž ˆŽ Š Šƒ ˆ Š Ž Ž ƒ Š Ž Ž ƒž ƒ ƒ ˆ ƒž Š Šƒ Š Ž ŽŽ ˆ ƒ ƒ Žƒ Ž Š Š ˆƒ d
5 Ž ƒ ƒ ˆ ƒž Š š ˆƒŽ Š Š ƒ ƒž šš Š Š š Š Š Š Ž Š ƒ š ƒ Ž Ž Š ˆ Šƒ Ž ˆ Ž ƒž ƒ Š ŠŽ Š ƒ ƒ Ž Š ƒ ƒ Š ƒ Š ƒžž ˆ ƒ ƒžž Š ƒ ƒ Š ƒœ ƒžž Žƒ ƒ Š ƒ ƒˆ ƒžž ƒ Š Š Ž ƒ ˆƒ Šƒ ƒ ƒ ˆ ƒ ƒ ƒ ˆŽ Š Š Š Ž Ž Ž ˆŽ ƒ Ž Žƒ ƒ Š ƒœ ƒ Š ŠŽ Ž Šƒ Š ƒ ƒž Š Ž ˆ ƒ Š ƒ ˆ ƒ Š ƒ ƒ Š Š š Šƒ Ž ˆ ƒž Ž ƒ Ž ƒ ŽŽ Š ƒ Š Šƒ ƒž Š ƒ š Ž ƒ ˆ ƒ ƒ ŽŽ ƒˆ ˆ ƒ Ž ŽŽ ƒ ˆ ƒ Š ƒ ˆ ˆ ƒ ƒ ƒžž Š Ž ƒžž ƒ ƒžž ˆ Ž ƒ Š Š œ Šƒ Š Š ƒ ŽŽ Š Šƒ Ž ˆ Ž ƒ ŽŽ Š Šƒ ƒ Ž ƒž Ž ƒ Š Ž ƒ Š Ž ƒ ƒ d
6 Š ƒ Ž ƒž ƒ œ Ž ƒž ƒž ƒ Š ƒ ƒ Žƒ ˆƒ ƒ Ž ƒ ƒ ƒ ƒ ƒ Š ƒ ƒ ƒ Ž ƒžž ˆŽƒ Ž ƒ ƒ šƒ ˆ ŽŽ ƒ Š ˆ Š Ž Ž ƒ Š ƒž ƒ Š ƒžž ƒ Š ƒž Ž ƒ Ž Ž Ž ƒ Š ˆ Šƒ ˆƒ ƒ Ž ˆ Šƒ Š Š ƒ ŽŽ Žƒ Š Ž ƒ ŽŽ Ž Š ˆ ƒ š ƒž Šƒ Š Š Š Žƒ Š Š ƒ Š Ž ƒž Žƒ Šƒ Š ƒ Š ƒ Ž Š Ž ƒ Š ƒ ƒ ƒ ˆ Ž ƒžž Ž ƒ Š ƒ ƒ ƒ Š Ž ƒ š Ž ƒ Ž Ž ˆ Š Ž Ž ƒž Ž ƒž ƒž ƒ ƒ œ Š ƒ ƒ Ž ƒ Š ƒ Š Ž ƒ ƒž Š ˆ Ž Ž Ž ƒ Ž ˆ Š Š ƒ ƒ ƒ Ž ƒžž ƒ ƒ Žƒ ƒ ƒžž Š ƒ Š ƒ Š Ž Ž ƒ Š ˆƒ ƒ Ž ƒž Ž Š ƒ ƒž ˆ ˆ ƒ ƒ ƒ ŽŽƒ ˆ Š d
7 ƒ ƒ Š ƒ ƒ ƒž ƒ ƒ ƒ ƒ Š Š Žƒ ƒ ˆ Ž ƒ ƒ Š Š ƒž ƒ Žƒ ˆ ŽŽ ŽŽ Ž ƒ Ž ƒ Ž ƒ ƒ ŽŽ ˆ ƒ Žƒ ƒ Ž Ž ƒ ŽŽ ˆ ƒ Š Š ƒ ŠŽ ˆŽ Ž ƒ Šƒ ƒ ƒ ƒ Š ƒ ˆƒ Ž œ Š Žƒ œƒž Š Ž š ŽŽ Žƒ Ž Š Ž ƒž Š Š Œ ƒ ƒ ƒ ƒžž Š ƒ Œ ƒ ƒ ƒ ƒ ƒ ƒž œ Šƒ Ž ŽŽ ƒ Ž ƒ ƒ ˆ ƒ Žƒ ƒ ƒ Ž ƒ Ž Šƒ Ž Žƒ Š ƒ Š ƒ ƒ Ž ƒ šƒ Ž ˆ ƒ Š Ž ƒ Ž Š œƒ ƒ Ž Žƒ ƒ ƒž ƒ Š ƒ ƒž ƒ Ž ŽŽƒŽ Ž Ž ƒ ˆ š Š Šƒ Ž Žƒ ƒžƒ ƒ ƒ Ž Š ƒ ˆ ƒ ƒ ƒž œ Š Š Ž ƒ ˆ ˆ Š ƒ ƒ ƒž ƒ ˆƒ Ž Ž Žƒ Žƒ ƒ Ž ƒž Ž ƒ Šƒ ƒ ˆ ƒž ƒ e
8 Ž ƒ ƒ ƒ ƒ ƒ ƒ ˆ Š Ž Žƒ ƒ ƒ Š Ž ƒ ƒ ƒ ƒƒ ƒž Š ƒ Š ƒ ƒ Ž ˆƒ Š ƒ ƒ Ž ˆˆ ƒ Ž ƒœ Š ƒ Ž ƒ ƒžž ƒ Š ƒ Ž Š ˆ Š Š Žƒ ˆ ƒ ƒžƒ ƒž Ž ƒž Š Ž ƒž ƒ Ž Š Š ƒ ƒ ˆ ƒž ƒ ˆ ƒ ƒ ˆ ƒ ˆ Žƒ ƒ Š Ž ƒžƒ ƒž ƒ Ž Žƒ ƒ ƒž ƒ Žƒ ˆ ƒ Š ƒ ƒ ƒ ƒžƒ ƒž ƒž ˆ ˆˆ ƒ ƒž ƒ ƒ Š šƒ ƒ ˆ ˆˆ ƒ ˆ ƒ ƒ ƒ Ž ƒ œ Ž ƒžž ƒž ƒ ƒ Š ƒ Žƒ Š ˆˆ ƒ ƒ Š Ž Ž Š ƒ ŽŽ Žƒ Š ƒ ƒž œ ŠŠƒœƒ ƒ ˆ š ƒžšƒœƒ Ž Šƒ ƒ Œ ˆ ƒ ƒ ƒ ˆ ˆ ƒ Ž Ž Š ƒ ƒž Ž e
9 Ž ƒ Šƒ ƒ Š Ž ƒ Ž Š ƒ ŽŽ Žƒ Š ƒ ƒ ƒžž ƒ Šƒ ƒ ƒ ˆ ƒ ƒž ˆ Š ƒ Ž ƒž ƒž ƒ ƒ Ž ˆ ƒ ƒ ƒž œ Š ƒ ƒ ˆ ƒ ƒ ƒž œ ƒ Š ƒ ˆƒ ƒ Š ƒ Ž ƒ Š ŽŽ Ž ƒ Š Š ƒ ƒ ƒ Š ƒ Š Žƒ ƒ ƒ ƒ ƒ ˆ ƒ ƒž ƒ ƒ ˆ Š Žƒ ƒ ƒ Š ƒ ƒ Š ƒ ˆ ƒ ƒ Š ƒ Š Ž ƒ ƒ ƒ ƒ Š ƒ ƒ Ž ˆ ˆ Š ƒ ƒ ˆ Š ƒ ƒ ƒ Žƒ Ž ˆ ƒ ƒž Š Ž ƒž Šƒ ƒ ˆ Š ƒ ƒžƒ Š ˆƒ ƒ Ž ƒ Ž Ž ˆ Š ƒžƒ Š ƒ Ž Š Ž ƒ ƒ Š ƒ Š ˆ Š ƒ Š Š ƒ ƒ š ƒ Ž Š Š ˆˆ ƒ Š ƒ š ƒ Š Ž š ƒ Š ƒ ŽŽ ƒ Ž ˆˆ ƒ e
10 Š Š Ž ƒž ˆ Š Š ƒ Š ƒ Ž Žƒ ƒ Š ŽŽ ƒ ƒ ˆ ƒ ˆ ƒž ˆ Š ƒ ˆ Š ƒ Š Š ƒ Ž ƒžž ƒ ƒ ˆŽ ƒ ŽŽ ˆ Š ƒ Ž Ž ƒ ƒžž ƒ Š ŽŽ Š Š ƒžžˆ ƒ ƒ ˆ ŽŽ ƒ Ž Ž Š Š ƒ Ž ƒ Žƒ Ž ˆ ƒ ƒ ƒ ˆŽ ƒ ƒ Š Ž ƒ ƒžž ƒ ˆ Š Š Š ŽŽ ƒ Š Ž ƒ ˆ ƒ Š ˆ Ž ƒ Š ƒ Ž ƒ Ž Š ƒ Š ŽŽ ƒ ƒ ƒ Š ŽŽ Šƒ Š ƒ ŽŽ ƒ ƒ ˆ ˆ Š ƒ ˆ Š Šƒ Ž ƒ ŽŽ Š ŽŽ ˆ Š ŽŽ Š ƒ ˆ Š ƒ Š ƒœ ˆ ŽŽ ƒ Ž Ž ƒ Š Ž Š Š Š Žƒ ˆ Š ŽŽ ƒ Ž Š ƒ ŠŽ ƒ ˆ ƒ Ž ˆ Šƒ Š ŽŽ ƒ Ž Ž ƒ Ž ƒ Š e
11 ƒžž ˆ Š Š ŽŽ ƒ Ž Žƒ Š ƒ Šƒ Šƒ ƒ œ Š Ž ƒ ƒ Ž Š Š Žƒ šš ƒ ƒ ƒ ƒ Š ŽŽ šš Š ƒ Š Ž Š Š Š ŽŽ Š Š Š šš ŠŽ Š ƒ Šƒ Š ŽŽ Š ƒ ƒƒ Š Š Š Š ŽŽ ƒž ƒ Ž ƒ Š ƒ ƒž Žƒ Ž Žƒ Šƒ ƒ ƒžž Š Š ˆ ƒ Žƒ Š ƒ ƒž ƒ Ž Ž Š Š ŽŽ ˆ Š ƒ Š ŽŽ ƒ Ž ƒ Š ƒ Š Ž ƒ ˆ ƒ ƒ Ž Š Š Š Žƒ ƒ Ž Ž ŽŽ ƒ Ž Žƒ Ž Š Žƒ ƒ Ž Ž Š ƒ Š ˆ ƒ ƒ Š ƒ Š ƒ Š Š Š Ž ƒ ŽŽ Žƒ ƒ ƒ ŽŽ ƒ ƒž šš ŠŠ Š Š ƒ ˆŽ Šƒ Š Š Žƒ ƒ Š Šƒ ƒž ˆ ˆ Š ƒ Š ŽŽ ƒ Ž ƒž œ ƒž ˆ ŽŽ ƒ Š Š ˆ ŽŽ Žƒ ƒ Ž ƒ ˆ dd
12 ŽŽ ˆ ˆ Š ƒ ƒ Š Š ƒ Š Š Žƒ Ž ƒ Ž ˆ ƒ Ž ŽŽ ƒ ƒ Š ƒ ˆ Š ƒ Š ŽŽ Š Šƒ ƒ ƒ ˆ Š ƒ Š ŽŽ ƒ Ž Ž ƒ ˆ Š ƒ Š ƒ ƒ Š Ž ƒ ƒž Ž ƒ ŽŽ Ž Ž ƒ ƒ Šƒ Ž ƒ ŽŽ Ž ƒ Š Ž ƒ Š Š ƒ Š Š ƒ ƒ Š ƒ ƒ Š ƒž Ž ƒ Ž ƒ Šƒ ƒ ˆ Š ƒ ƒ ƒž ƒ ˆ ƒ Ž ƒ ˆ Š ƒ ƒ Šƒ ƒ ƒ Žƒ ˆ Šƒ ƒ ƒž ƒ Ž ƒ ƒ Š Š Ž š Šƒ Š Š Ž ƒ ŽŽ Ž ƒ ˆ Š ƒ ƒ ƒ Žƒ Ž ˆ ƒž Šƒ ŽŽ ƒ Ž Š ƒ Š šƒ Ž Š ƒ ƒ ƒ Š Š Š Š ŽŽ š Ž Ž Š Š ƒ Žƒ Š ƒ Ž ŽŽ ˆ Š Š Š dd
13 ƒ ƒ Ž ˆ ˆ Š ŽŽ ˆ Š ƒ ƒ Š ƒžžžƒ ƒ Š ŽŽ Šƒ Š ƒ Ž ƒ Š Š Ž ƒ ŽŽ ƒ ƒ ƒ Š ˆ Š ƒ Žƒ ƒ ƒ Š Š Ž Žƒ Šƒ ƒ ƒ ƒ ƒž ƒ Šƒ ƒ ƒ Ž ŽŽ ˆ Š ƒ Š ƒž ƒ Š Š Ž ƒ Žƒ ƒž Šƒ Šƒ Š ŠŽ Ž š Šƒ Ž ƒ Ž ƒ Ž Š ƒ Š Š Š ŽŽ Šƒ ƒ Š Ž Ž ˆ Š ƒ Š ŽŽ ƒ ˆ ƒ Š ƒ Žƒ Šƒ ƒ Š ƒ Š Š Š ŽŽ ƒž Ž Ž Šƒ ƒ ˆ Ž Žƒ Ž Ž ˆ ƒ ƒ Šƒ Š ƒ Š Ž ƒ Š ƒ ŽŽ Š Žƒ Š Ž Š ƒ ƒ Š ƒ Šƒ Š Š Ž Žƒ Žƒ Žƒ ƒ Š ƒ ƒ ˆ ƒ Ž Ž ƒ ˆ ƒ Šƒ Š Š Ž Žƒ Š ƒ ƒ Š CD38 ŽŽ ŽŽ ƒ Ž Š ƒ ˆ Š ƒ Š Š Š dd
14 Ž Žƒ Žƒ Š ƒ Š ƒ ƒ ˆ Š ƒ Šƒ Š ƒ Š Š ƒ š ˆ Š ƒ phenotype present in the leukemia also showed a correlation Š ƒž ƒ ˆ ƒ Ž ˆˆ ƒ ƒ Ž ƒ Š Š Ž ƒ ƒ Ž Š ƒ Šƒ Š Š ŽŽ ƒ Š Š ƒ ƒž ƒ ˆ ƒ ˆˆ ƒ Ž ƒ Š ƒ Ž Š ƒ Ž ƒ ƒ ƒ ƒ ˆ ƒ Š ƒ Ž Ž ƒ ŽŽ ƒ Š Š ƒ Š Š Ž ƒ ŽŽ Ž Š Šƒ ˆ ƒ Žƒ Œ Ž ŽŽ Š š ƒ ƒ ƒ ƒ ƒž œ Š ƒ ˆ ƒž Š ƒ ƒ ˆ ƒž ŽŽ ƒ ƒ Žƒ Š ƒ Š ƒ Ž ŽŽ ƒž ŽŽ ˆ Š ˆ Š Š ƒ ƒ Š Š ˆ Š ƒ Š ŽŽ ƒ ˆ ƒ Š ŽŽ Š šƒ Š ƒ ˆ ˆ ŽŽ ƒ Š ƒ Š Š ƒ Š Š ƒ ƒ Ž dd
15 Š ˆ Š ƒ ƒ ˆ ƒžž ƒ ƒ Š ƒž ƒ ƒ ˆ Š ƒ ƒžž ƒ Ž ŽŽ ƒ ˆˆ ƒžž ƒ ƒ Ž ˆ Š Ž ƒ Š ˆ Š ƒ Š Š Š Ž ƒ ŽŽ Š ƒ Š ƒ ƒžž ƒ ƒ ƒž ƒ ƒ ˆ ƒ Ž Žƒ Ž ˆ Š ƒ ˆ Š ƒ ƒžž ƒ ƒ ƒ ƒ ƒž ƒ ƒ ˆ Ž ƒ Ž ƒ Š ˆ Š ƒ Š ƒžž Š ƒ ƒ ƒ Ž ƒ Š ƒ ˆˆ ˆ ƒ Ž Š Ž ƒ ŽŽ ƒ Š Š Š Ž ƒ ŽŽ ƒžž ƒ ƒžž Žƒ Ž Š ƒž ƒ Ž ƒ Ž ƒ Š ƒž ƒ Ž ƒ Š Ž ƒ ŽŽ ƒ ˆ Š ƒž ƒ Ž ƒ Š ƒžž ƒ ƒž ƒ ƒ ˆ ƒ Ž Š ˆƒ Ž ˆ Ž ƒ Ž ƒ Žƒ ƒ š Žƒ Š ƒ ƒ Š Ž ƒž Ž ƒ ˆ ƒ Š ˆ ˆ ƒ Ž ƒ ƒž Šƒ Š Šƒ Ž ƒ ŽŽ ƒ ƒ Šƒ ˆ ƒ ˆ ƒ dd
16 Ž ƒž Ž ƒ ˆ ƒ Š ƒ ˆ ƒ ƒ Ž ƒž ƒž Š ƒ ƒ ƒ Ž Š ƒ Ž ƒž Žƒ Ž ƒ ŽŽ ƒ ƒ ƒ ƒ Žƒ Š š Ž ˆˆƒ ƒ Ž ˆ Š ƒž Š ƒ Š Ž ƒ Š Š Š ƒ Žƒ ƒ ƒž œ Ž ƒž Š Ž Š ˆ Š ˆ Š Ž Š š ˆŽ ŽŽƒ ƒ ƒ ˆ Šƒ Š ƒ Š ƒ ŽŽ Žƒ Š Ž ƒ ŽŽ ƒ Š ƒ ˆ Šƒ ˆ Š Š ƒ Žƒ Ž ƒ Šƒ ƒ Ž Š ƒ ƒ Š Ž Ž ƒ Š ƒ Š ƒ Š ˆ Š ˆ Š Ž ƒž ƒ ˆ Š ƒ ƒœ ˆ ƒ Šƒ Ž ƒ ŽŽ ƒ ƒžž ƒ ƒž ˆ ƒ ƒ Šƒ Š ƒœ ˆ Ž ƒžž ˆ Š ƒ Šƒ Ž ƒ ŽŽ Šƒ Ž ƒ ƒ ˆ ƒž Š Ž ƒ ˆ ˆ ƒ ˆ Šƒ Š Š Ž ƒ ŽŽ Š ˆ ƒ ƒ Ž Ž Šƒ ƒ ƒ Šƒ ƒ ƒ ƒžž Ž Šƒ ˆƒ Š Šƒ Š Š ƒ ƒ Ž Š ˆ Š Š Ž ƒ ŽŽ ƒ ƒ ƒ Šƒ ˆ ƒ Ž Ž ƒ Š ˆƒ ƒ Ž dd
17 ƒ ƒž Ž ˆ Š Š ƒ Š Š Š Ž ƒžž ˆ Š ƒ Š ƒžž ƒ ƒž ƒ ƒ ˆ ƒž Šƒ ƒž Š Š ƒ ˆ ƒ ˆ ƒ Š ƒ ƒ Šƒ ƒ Ž ƒ ŽŽ Ž ƒ ˆ Š Šƒ ƒž Š ŽŽ Š ƒ ˆ Š ŽŽ ƒ ƒ š Ž Ž Š Š ƒ Žƒ Š Ž ƒ Š Š ŽŽ Š ƒ Ž Ž ƒž ƒž ƒ ˆ Š ƒ Š Žƒ ƒ Ž ŽŽ ƒ ƒ Š ƒ ƒ ƒ Ž ƒ ƒž Š ŽŽ ƒ ƒ Š Šƒ ƒž ˆ Š ƒ Š Š ŽŽ Ž Šƒ Š Š ŽŽ Š Šƒ Šƒ š ƒ ƒ ˆƒ ˆ Š ƒ ƒ Š ƒžž ˆ Š ƒ Š ƒ Šƒ Š ƒ Žƒ ƒ ƒž ˆ ƒ Š Š ˆ Š ƒ Šƒ Šƒ ƒž Š ƒž ˆ Šƒ ƒ Š Š ŽŽ Žƒ Ž ƒ ƒ ƒ ŽŽ ƒžˆ Šƒ Š ƒ ƒ ŽŽ ƒ Š ŽŽ ƒ ˆ Ž ŽŽ ˆ Š ƒžž Š ƒ ƒ Žƒ Šƒ ƒž ˆ Š ƒ Š ŽŽ de
18 ˆ ƒžž ƒ ƒ Š ˆ ˆ Š ƒ Šƒ ƒ ƒ Š ƒ ƒ Šƒ Š ƒ Ž ŽŽ ƒ ƒ Š Ž Šƒ Š ˆˆ ƒ š Žƒ Š ˆƒ Šƒ ƒ ŽŽ ƒž ˆ ˆ ƒ Žƒ Šƒ ˆ Š ƒ Š Šƒ ŽŽ ƒ Ž ŽŽ Š ƒžž Žƒ ˆ ŽŽ Š ƒ ƒ ˆ Š ƒ ƒžž ˆ Š Š ŽŽ Šƒ Š ƒ Šƒ Šƒ ƒ œ Š ƒ Ž ŒŽ ƒ ƒž Ž Šƒ ƒž Š Š Š ƒ ƒœ ˆ ƒ Š ŽŽ Š ƒ ƒ Žƒ ŽŽ ƒ ƒžž Šƒ Žƒ ŽŽ Žƒ Ž Ž Šƒ Š Š ŽŽ ƒ ƒ Ž Ž Ž Š ƒ Š Ž ƒ ƒ Š ƒ ƒ Š ƒ Š Ž ˆ Š Š Š ŽŽ Ž Šƒ Š ƒžžž Žƒ ˆŽ ƒ ƒ ƒž Ž ˆ Šƒ Š Š Š ŽŽ Šƒ Žƒ Žƒ Ž ƒžš ƒ Š ƒ Žƒ ƒ Ž Š Š ˆ Š Š ƒ ŽŽ ˆ Šƒ ƒ Ž Ž ƒ ˆ ƒ Žƒ Š ƒ de
19 ƒ ƒ ƒ Š Ž Šƒ Š ƒ Š Ž ƒ ƒ ƒˆ ˆ Š ƒ ˆŠ ƒ ˆˆ ƒ ƒ Š Š Š Ž ƒ Ž Š Šƒ Ž ƒ ŽŽ Šƒ ƒ Š Š ƒž Š Š Šƒ Š Š Ž ƒ ƒ Š ƒ Šƒ ˆ ˆˆ ƒ Š ƒ Š ƒ Š ƒ Š ˆ Š ˆƒ ƒ Ž ƒ Š Š ƒ ƒ Ž ƒ ƒž š ˆˆ ƒ Š ƒ Š ˆ Šƒ Š Ž ƒ Ž Š ƒ ŽŽ Žƒ Š Š ƒ ƒ ƒ ˆ ƒ ˆ ƒ ƒ ƒ ˆ ƒ Žƒ ƒ ƒž ˆƒ ƒ Š Š ˆƒ ƒ ƒ ƒ Žƒ Ž ˆ ƒ Š ƒ Š Ž ƒ ŽŽ ƒ ƒ Ž ƒžž ƒžž ƒ ˆŽ Š Š ˆ ƒ ƒ ƒ ˆ ƒ ƒ ƒ Žƒ Ž ˆ Žˆ ƒ Šƒ Š Š Ž ƒ ŽŽ Š Š ƒ ƒ ˆ Š Š ƒ ˆ ˆ ƒ Š Š ƒ Ž Š Š Š Š ˆ Š Š Ž ƒ ŽŽ Š ƒ ƒ ƒž Š ˆŽ ƒ ˆ Š Š Š Žƒ ƒ ƒ ƒžž Š Ž Š Ž ƒ Ž Š ˆ Š ƒ ˆ ƒ Š Š Š ŽŽ Š ƒ ƒœ ˆ Š ŽŽ ƒ Šƒ Š Š ƒ ƒ Š Ž ƒ Ž de
20 Š Ž Š Ž Š Š Ž ƒ ƒžž ƒ ƒ ƒ ˆ Š ƒž ŽŽ ƒ Ž Š Šƒ Ž Š Žƒ ˆ Š Ž ˆ Š ƒ ˆƒ Š Š Ž ƒ Š ƒ ˆ ƒ ˆ Š ƒ Ž ƒžž Š ƒ Ž ƒ Ž ƒž ƒž Ž ƒ ƒ Š ƒ Š Š Ž Š Ž ƒ ƒ ƒžž Š ƒ ƒž ƒ de
21 Ž Š ƒ Š Šƒ Š ƒ Š ƒ Š ƒ Ž ƒ Š ŽŽ ƒ Š Ž ƒž ƒžƒ ƒ Ž Šƒ ƒ ƒ Ž ƒ Š ˆ Šƒ Ž ƒ ƒ œ ƒ Ž Š ƒ Š Ž ƒ ƒ ƒ Žƒ ƒ Š ƒž Š Žƒ ƒ Ž ƒž ˆˆ ƒ ˆˆ ƒ ƒ ƒ Š Š ƒœ ƒ ƒž Š ƒ šƒ Ž ƒ Ž Šƒ Ž ƒ ƒ ƒ Ž ƒ Ž ƒž Š ƒ Š ƒ ƒž ƒ ƒ Ž Š Š Šƒ Ž ƒ Š ˆ ƒ Š Ž ƒž ƒ Š ƒ Š ƒˆˆƒ Š Š Žƒ Š ƒ ƒ ˆƒ ƒ ƒ Š ƒ ƒ ƒ ƒž ŽŽ Ž ƒž ƒ Š ƒ dd
22 Š Š ƒ Š ƒ Šƒ Š ƒ ƒžž Š ƒ Š ˆ Š ƒ Š ƒ ƒ ƒž œ Š ƒ ƒ ŽŽƒ Š Šƒ ƒ ƒ Š ˆ Š ˆ ƒž ˆ Š ƒ dd
23 ˆ ƒ ƒ ƒž ŽŽ ƒ Š ƒ ƒ Ž Ž ƒ ƒ ƒˆ ƒ Žƒ ƒ ƒ ƒ ƒ Ž Ž ƒ ƒ œ ƒ ƒš ƒ Š Šƒ ƒ ˆ ƒ Š ƒ ŽŽ ƒ ƒ Š ƒž ƒ ƒ Ž Ž ƒ ŽŽ ƒ ƒ ƒ Š Š ƒ ƒ ƒ ƒ ˆ Ž ƒ ƒ ƒˆ ƒ ƒž ƒ ƒ ŽŽ ˆ ƒ Ž Ž ƒ ƒ Š ƒ Ž Š Š ˆ ƒ Ž ƒ ƒ ƒ ƒ ƒž ƒˆ Š ƒ ƒ ˆŽ Š ˆ Ž ƒ ˆ ƒ ˆ Š Š ˆ Ž Š Š ƒ ƒž ƒ Ž ƒ Ž ƒ Ž Ž ƒ ˆˆ Š ƒˆ ƒž Œ ŒŽ ƒ Ž ƒž ŽŽˆ ƒ ƒ ˆ Ž ƒž ƒ Ž Ž ƒ Š ƒ ƒž Ž Š Š ƒ ƒ Ž Žƒ ˆ ƒ ˆƒ Ž Ž ƒ Šƒ ƒ ƒˆ ƒž ƒ dd
24 ƒ Ž ƒ ŽŽ ƒž ƒˆ ˆƒ Ž Ž ƒ ˆ ƒ ƒ ƒž ŽŽ ŽŽ Šƒ ƒ ƒ Š Šƒ ƒ ˆƒ Ž Ž ƒ Šƒ ƒ ƒž ƒ Š ƒ ƒ ˆ Ž Šƒ ƒ Š ƒ Š ƒ ƒˆ ˆŠ ƒ ƒ Ž Ž ƒ ŽŽ ƒ Ž Ž ˆ ƒ ƒ ˆ Š ƒ Šˆƒ ƒ ƒ Ž ƒ Š ˆ ƒ ˆ ƒ ƒ Ž Š ƒˆ ƒž ˆŠ ƒ ƒ Ž Ž ƒ Š ˆ Š ƒ Š ƒ Ž ƒ Š ƒ ƒž Ž ƒžž Ž ƒ Žƒ ˆŽ ŽŽ ƒ Ž Ž ƒ Ž Š ƒ ƒ ŽŽ ƒ ƒž ƒž ƒ ŽŽ œ ƒ ƒž ŠŽ Ž ˆ Ž Žƒ ƒ ˆƒ ƒ ƒ Ž Ž ƒ ƒ ƒžƒ ƒ ƒ ƒ Ž ƒ dd
25 Š Š Ž ƒž ƒžš ƒ ŽŽ Š Š ƒ Šƒ ƒ ƒ Š Š ƒ Ž Ž Šƒ š Ž ŽŽ ƒ ƒ ƒž Š ƒ ˆ ŽŽ Š ƒ ƒ ˆ ƒž Ž ƒ ŽŽ ƒ ƒ ƒ ƒ ƒ ƒž Šƒ ƒ œƒ ˆ ŽŽ ŠƒŠ Š ƒž Š Š ƒ ƒ ˆ Ž ƒ ƒ Ž Ž ƒ ƒ Ž ŽŽ ƒ Š Š ƒž Ž Š Š ƒ ƒ ƒ ƒ Ž ƒ ŽŽ ƒ ƒ Š ŽŽˆ ƒ ƒ Žƒ Šƒ Ž ƒž š ƒ Ž ƒ Š ƒ ƒž ˆŽ ƒ ŽŽ ƒ ƒ ƒ ƒ ˆƒ Ž Ž ƒƒ Š Ž ƒž ˆ ƒ š ƒ Ž ŒŽ ƒ Ž ƒž ˆŽ ƒ ŽŽ ƒ Ž Ž ƒ ƒ ˆŠ Š ƒž ƒž ƒ Š ƒ ƒ Ž ƒ ƒ Š Š ƒ Ž Ž ƒ ƒ ƒ Žƒ ˆ Š ƒž Ž ƒžƒ ˆ ƒžˆžƒ Ž ƒ ƒ ƒ šƒ ˆ ƒ Ž Š Ž ƒ ƒ Ž Ž ƒ dd
26 Žƒ ˆ ƒž ƒ œ Ž Šƒ ˆˆŽƒ Ž ƒž ƒ ƒ ƒ šƒ ƒ ƒ ƒ Ž ƒ ƒ Ž Ž ƒ ƒ ƒ Ž ƒ ƒž ƒž Šƒ ƒ œƒ ˆ Š Ž Ž ƒ ŽŽ ƒ Ž Š ƒ ƒž ƒ ƒ ƒ ƒ ˆƒ Ž Ž ƒ ƒ Ž ƒ ˆ ƒ ƒ ƒž š ƒ Ž ŠƒŽˆ ˆ Š ƒ ƒ Ž ƒ Žƒ ƒ ƒ ˆ ƒ ƒž ƒ ˆ ƒ ƒž ƒ ƒ Š ƒ ƒ ƒ ƒ ƒ ƒ Žƒ ˆŠ ƒ Š ƒ ŽŽ Žˆ ƒž Š Ž ˆ ƒ ƒž ƒ Ž ƒ ƒ ƒž ƒ ˆ Š ƒ ˆŠ ŠŽ Š ƒžƒ Š Ž Ž ƒ ƒ ŽŽ Žƒ ƒ Œ ŽŽ ƒž Žƒ ˆ Š ƒ Š ƒ Š ƒ ˆƒŽ Š Š ƒ ƒ ƒ Ž ƒ ƒ ƒ Ž ƒ Ž ƒ Ž ƒž Ž Ž dd
27 ƒ ƒžƒ ƒž ˆƒŽ Š Š ƒ ƒ Ž ŽŽ Ž ŽŽ ƒ ƒž Šƒ ƒ œƒ ˆ Ž Š Š ƒ ŽŽ Žƒ Ž ˆ ƒ Ž ƒ Ž ŽŽ ƒž ˆ Š ƒž Ž ƒ ˆ ŽŽ ƒ Ž Ž ƒ ŠŽ ƒ ˆ ŽŽ ƒ ƒ Ž ƒ Ž ƒ ƒ ƒ ƒž ƒ ƒ Ž Ž ƒ Ž Š ƒž ƒ ˆ Š ƒ ƒž ˆ ƒ ƒ ƒ œƒ ˆ ƒ ƒ ƒ ƒ ƒ ˆ Š ƒ ƒž Ž ƒ Ž Ž ƒ ƒ ŽŽ ƒ ƒ ˆ Ž Šƒ ƒž ŠŽ ˆ Š ƒ ŽŽ ƒ ƒ ƒ ƒ Ž ƒž ƒ Ž Ž ƒ Ž ƒ Š ƒ Ž ƒ Šƒ š ƒ ƒ ƒ Š ƒ Ž Ž ƒ ƒ Š Ž de
28 Š Š ƒž š ƒ ƒ Š Ž ƒž ƒ Šƒ Ž Ž ƒ ƒ Ž ƒ ˆƒ œœ ƒž ƒ ƒž ˆ ƒ ƒž ˆ š ƒ ƒžž Žƒ ˆƒ Ž Ž ƒ ŽŽ ƒ Ž Š ƒ Ž ƒ Š Ž Šƒ Š Ž ƒž Šƒ ƒ ˆ ƒ Ž ƒ Ž Ž ƒ Ž ƒ ŽŽ Š ƒž ŽŽ ˆ Š ƒ Šƒ Žƒ ƒ Ž Š ƒ ƒ Ž ƒ Ž ƒž ƒ ƒ ƒ ˆ ƒ Š ƒžž ƒž ƒ Ž Ž ƒ Š Šƒ Š ˆƒ ƒ Ž ˆƒ ƒ Ž ƒ ƒ Ž ƒ de
29 ƒ Ž Ž ƒžšƒ ƒ ˆƒ Ž ƒž ƒž ƒ ƒ ƒž ƒž Šƒ ƒ Š Š Š Š ƒ ƒ ƒ ƒ ƒ ƒ ƒž Ž š ƒ ƒž ƒ ƒ ƒ ƒ ƒ Žƒ ƒ ƒ Ž ƒ ƒ de
30 Ž ƒ ƒ ƒ ƒ ƒž ƒž Šƒ ƒ Š Š Š Š ƒ ƒ ƒ ƒ ƒž Ž ƒž Š Š ƒ ƒ Ž ƒ Ž Š Ž ƒ Ž Ž ƒ Ž Žƒ Ž Ž ˆ ƒ ƒ ˆŽƒ Ž ƒ ƒ šƒ ˆƒ ƒ Ž Ž ƒ Š Ž Ž Š ƒ Ž ƒ ƒ de
31 ƒ Ž Šƒ ƒ œƒ ˆ Š ƒ Š Š Ž ƒ ƒ Š Š CD # CBF CD34 + CD38 - ALDH high NA CD34 + CD38 - dual ALDH int high /ALDH ƒ Ž Ž ƒ ƒž Š Š ƒ ƒ š ˆŽ Š œƒ ˆƒ ƒ Ž Ž ƒ ˆ ƒž ŽŽ ˆ ƒž ŽŽ ŽŽ ƒ Ž Š ƒ ƒ ƒ Ž ƒ Ž ˆ ƒ Šƒ dd
32 ƒ Ž Ž ƒž ˆ ƒ Ž ƒ Š ƒ ŽŽ Žƒ Š CD34 + CD38 - ALDH high (including dual) ƒž (n=33) (n=43) Complete remission 15/33 (45%) 29/43 (67%) 19/22 (86%) Median OS (months) 9.4 HR HR 1 Not reached 0.02 Median EFS (months) AlloBMT in CR1 Continuously EF Median EFS (months) 8/15 (53%) 5/8 (63%) Not reached 16/29 (55%) 7/16 (44%) Not reached 6/20 (30%) 5/6 (83%) 23.1 (95% CI: 23 35) 0.2 No BMT in CR1 Continuously EF Median EFS (months) 7/15 (47%) 0/7 4.6 (95% CI: 3 32) 13/29 (45%) 4/13 (31%) 11.9 (95% CI: 5 32) 13/20 (65%) 7/13 (54%) Not reached 0.06 ƒž Š Š ƒ ƒ š Žƒ ƒ Š ˆ ˆ ƒž ƒžž ƒž ƒžž ƒžž ƒ ƒ Žƒ ƒ ˆ Ž Šƒœƒ ƒ ˆ ƒž ƒž ˆ Š šƒ dd
33 ˆ ŽŽ ˆ ƒ ƒ ƒ ƒ Š ŽŽ ƒ ˆŽ ƒ ƒ ˆ ƒ Žƒ ˆ ƒ ŽŽ Š ŽŽ ƒ Š Š Š Š Š ŽŽ ƒ Š ƒ Ž ƒ ˆ Žƒ ŽŽˆ ƒ Š Žƒ Šƒ Š ƒ Š Ž Š ŽŽ š Ž Ž Žƒ Š Ž Žƒ ˆ ŽŽ ˆ ƒ ƒ Š ƒ ˆŽ ƒ ƒ ˆƒ ƒ Žƒ ˆ ŽŽ Žƒ ˆ ƒ ƒ ˆ Žƒ ŽŽˆ ƒ Š Žƒ ƒž Šƒ Š ƒ Š Ž Š Š Š ŽŽ ƒ š Ž Ž Žƒ Š Ž Š Š Žƒ ˆ ŽŽ ƒ ˆŽ ƒ ƒ ˆƒ ƒ Žƒ ˆ ŽŽ Žƒ ˆ ƒ Š Š Š ŽŽ ƒžž ƒžž ˆ Š ƒž ŽŽ ƒ ˆ Žƒ ŽŽˆ ƒ Š Š Š Žƒ Šƒ Š ƒ ƒ ˆŽ ƒ ƒ ˆƒ ƒ Žƒ ˆ ŽŽ Žƒ ˆ ƒ ƒ Š ƒž ƒ Š Š Žƒ dd
34 ƒ Ž ƒž ƒž Š ƒ Š ƒ Ž Ž ƒ ŽŽ Šƒ ƒ ˆ ŽŽ ˆ ƒ Š ƒ ˆ ƒ Ž ˆˆ ƒ Š Ž ƒ Š ƒ Š dd
35
36
37
38
39
40 CD34 - (<1%) (n=22) NPM1 mutation (n=14) NPM1 wild type (n=8) Normal cytogenetics (n=14) FLT3-ITD (n=3) Normal cytogenetics (n=4) t(9;11) (n=2) +21 (n=1) Complex karyotype (n=1) Supplementary Figure 2A. Diagram of cytogenetic /molecular characteristics for AMLs on clinical trial NCT with < 1% CD34 + cells in the diagnostic bone marrow.
41 CD34 + (>1%) (n=76) CD38 - ALDH int (n=43) CD38 - ALDH high (n=33) NPM1 wild type (n=37) NPM1 mutated (n=6) NPM1 wild type (n=31) NPM1 mutated (n=2) Normal cytogenetics (n=15) FLT3-ITD (n=1) Intermediate-2 Risk cytogenetics (n=9) Complex karyotype (n=8) Other Adverse-Risk cytogenetics * (n=5) Normal cytogenetics (n=2) FLT3-ITD (n=1) +8 (n=2) Der (7;13) (n=1) Complex karyotype (n=1) FLT3-ITD (n=1) Normal cytogenetics (n=8) FLT3-ITD (n=4) Intermediate-2 Risk cytogenetics (n=0) Complex karyotype (n=16) Other Adverse-Risk cytogenetics * (n=6) FLT3-ITD (n=1) Complex karyotype (n=2) FLT3-ITD (n=1) * Other Adverse-risk cytogenetics refers to patients with adverse-risk cytogenetics based on European LeukemiaNet Criteria but without complex karyotype. Supplementary Figure 2B. Diagram of cytogenetic /molecular characteristics for AMLs on clinical trial NCT with > 1% CD34 + cells in the diagnostic bone marrow. The ALDH high group includes 7 patients with dual ALDH int and ALDH high populations.
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