Article The proteogenomic subtypes of acute leukemia

被引：70

作者：

Jayavelu, Ashok Kumar ^{[1
,5
,6
,30
]}

Wolf, Sebastian ^{[2
,27
]}

Buettner, Florian ^{[3
,4
,7
,27
]}

Alexe, Gabriela ^{[8
,9
]}

Haeupl, Bjoern ^{[2
,3
,4
,27
]}

Comoglio, Federico ^{[10
]}

Schneider, Constanze ^{[2
]}

Doebele, Carmen ^{[2
,3
,4
]}

Fuhrmann, Dominik C. ^{[11
]}

Wagner, Sebastian ^{[2
]}

Donato, Elisa ^{[12
,13
,14
]}

Andresen, Carolin ^{[12
,13
,14
]}

Wilke, Anne C. ^{[2
]}

Zindel, Alena ^{[2
,3
,4
]}

Jahn, Dominique ^{[2
,3
,4
]}

Splettstoesser, Bianca ^{[1
]}

Plessmann, Uwe ^{[15
]}

Muench, Silvia ^{[2
]}

Abou-El-Ardat, Khali ^{[2
]}

Makowka, Philipp ^{[2
]}

Acker, Fabian ^{[2
]}

Enssle, Julius C. ^{[2
]}

Cremer, Anjali ^{[2
]}

Schnutgen, Frank ^{[2
,3
,4
,27
]}

Kurrle, Nina ^{[2
,3
,4
,27
]}

Chapuy, Bjoern ^{[16
,28
]}

Loeber, Jens ^{[16
,28
]}

Hartmann, Sylvia ^{[17
]}

Wild, Peter J. ^{[17
]}

Wittig, Ilka ^{[18
]}

Huebschmann, Daniel ^{[4
,12
,13
,14
,19
,20
]}

Kaderali, Lars ^{[21
]}

Cox, Juergen ^{[22
]}

Bruene, Bernhard ^{[11
]}

Roellig, Christoph ^{[23
]}

Thiede, Christian ^{[23
]}

Steffen, Bjoern ^{[2
]}

Bornhaeuser, Martin ^{[23
,24
]}

Trumpp, Andreas ^{[12
,13
,14
,29
]}

Urlaub, Henning ^{[15
,25
]}

Stegmaier, Kimberly ^{[8
,9
,26
]}

Serve, Hubert ^{[2
,3
,4
,27
]}

Mann, Matthias ^{[1
]}

Oellerich, Thomas ^{[2
,3
,4
,27
]}

机构：

[1] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Martinsried, Germany

[2] Univ Hosp Frankfurt, Goethe Univ, Dept Med 2, Hematol Oncol, Theodor Stern Kai 7, Frankfurt, Germany

[3] German Canc Consortium DKTK, Partner Site Frankfurt Mainz, Heidelberg, Germany

[4] German Canc Res Ctr, Heidelberg, Germany

[5] DKFZ, Clin Cooperat Unit Pediat Leukemia, Heidelberg, Germany

[6] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[7] Goethe Univ, Univ Hosp Frankfurt, Dept Med, Frankfurt, Germany

[8] Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA

[9] Boston Childrens Hosp, Boston, MA USA

[10] enGene Stat GmbH, Basel, Switzerland

[11] Goethe Univ, Dept Biochem 1, Frankfurt, Germany

[12] German Canc Res Ctr, Div Stem Cells & Canc, Heidelberg, Germany

[13] DKFZ ZMBH Alliance, Heidelberg, Germany

[14] Heidelberg Inst Stem Cell Technol & Expt Med HIST, Heidelberg, Germany

[15] Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, Gottingen, Germany

[16] Univ Med Ctr Gottingen, Dept Med Hematol & Oncol, Gottingen, Germany

[17] Univ Hosp Frankfurt, Dr Senckenberg Inst Pathol, Frankfurt, Germany

[18] Goethe Univ, Inst Cardiovasc Physiol, Funct Prote, Frankfurt, Germany

[19] Heidelberg Inst Stem Cell Technol & Expt Med HIST, Pattern Recognit & Digital Med, Heidelberg, Germany

[20] Natl Ctr Tumor Dis NCT Heidelberg, Mol Precis Oncol Program, Computat Oncol, Heidelberg, Germany

[21] Univ Med Greifswald, Inst Bioinformat, Greifswald, Germany

[22] Max Planck Inst Biochem, Computat Syst Biochem Res Grp, Martinsried, Germany

[23] Univ Hosp Carl Gustav Carus TU Dresden, Dept Internal Med 1, Dresden, Germany

[24] Dresden NCT UCC, Natl Ctr Tumor Dis, Dresden, Germany

[25] Univ Med Ctr Gottingen, Inst Clin Chem, Bioanalyt, Gottingen, Germany

[26] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[27] Goethe Univ Frankfurt, Frankfurt Canc Inst, Frankfurt, Germany

[28] Univ Med Berlin, Charite, Dept Hematol Oncol & Tumor Immunol, Campus Benjamin Franklin, Berlin, Germany

[29] German Canc Consortium DKTK, Heidelberg, Germany

[30] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

来源：

CANCER CELL | 2022年 / 40卷 / 03期

关键词：

ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION; FUNCTIONAL PREDICTIONS; COMPUTATIONAL PLATFORM; DATABASE; PROTEIN; HETEROGENEITY; AML; CLASSIFICATION; IDENTIFICATION;

D O I：

10.1016/j.ccell.2022.02.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none is exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is captured only in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival on treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired toward stronger complex I-dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.

引用

页码：301 / +

页数：30

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