Universität zu Köln

Grossmann, Vera, Schnittger, Susanne, Kohlmann, Alexander, Eder, Christiane, Roller, Andreas, Dicker, Frank, Schmid, Christoph, Wendtner, Clemens-Martin, Staib, Peter, Serve, Hubert ORCID: 0000-0001-8472-5516, Kreuzer, Karl-Anton, Kern, Wolfgang, Haferlach, Torsten and Haferlach, Claudia (2012). A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood, 120 (15). S. 2963 - 2973. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

The karyotype is so far the most important prognostic parameter in acute myeloid leukemia (AML). Molecular mutations have been analyzed to subdivide AML with normal karyotype into prognostic subsets. The aim of this study was to develop a prognostic model for the entire AML cohort solely based on molecular markers. One thousand patients with cytogenetic data were investigated for the following molecular alterations: PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, FLT3-ITD, and MLL-PTD, as well as mutations in NPM1, CEPBA, RUNX1, ASXL1, and TP53. Clinical data were available in 841 patients. Based on Cox regression and Kaplan-Meier analyses, 5 distinct prognostic subgroups were identified: (1) very favorable: PML-RARA rearrangement (n = 29) or CEPBA double mutations (n = 42; overall survival [OS] at 3 years: 82.9%); (2) favorable: RUNX1-RUNX1T1 (n = 35), CBFB-MYH11 (n = 31), or NPM1 mutation without FLT3-ITD (n = 186; OS at 3 years: 62.6%); (3) intermediate: none of the mutations leading to assignment into groups 1, 2, 4, or 5 (n = 235; OS at 3 years: 44.2%); (4) unfavorable: MLL-PTD and/or RUNX1 mutation and/or ASXL1 mutation (n = 203; OS at 3 years: 21.9%); and (5) very unfavorable: TP53 mutation (n = 80; OS at 3 years: 0%; P < .001). This comprehensive molecular characterization provides a more powerful model for prognostication than cytogenetics. (Blood. 2012; 120(15): 2963-2972)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grossmann, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnittger, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohlmann, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Eder, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Roller, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dicker, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendtner, Clemens-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Staib, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Serve, Hubert UNSPECIFIED orcid.org/0000-0001-8472-5516 UNSPECIFIED Kreuzer, Karl-Anton UNSPECIFIED UNSPECIFIED UNSPECIFIED Kern, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Haferlach, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Haferlach, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-481043
DOI:	10.1182/blood-2012-03-419622
Journal or Publication Title:	Blood
Volume:	120
Number:	15
Page Range:	S. 2963 - 2973
Date:	2012
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; COMPLEX ABERRANT KARYOTYPE; ACUTE MYELOGENOUS LEUKEMIA; FLT3 LENGTH MUTATIONS; SEQUENCING TECHNOLOGY; TANDEM DUPLICATION; ACQUIRED MUTATIONS; CEBPA MUTATIONS; TET2 MUTATIONS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48104