A novel hierarchical prognostic model of AML solely based on molecular mutations.
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.
MLL Munich Leukemia Laboratory, Munich, Germany.
Vera
V
Grossmann
Susanne
S
Schnittger
Alexander
A
Kohlmann
Christiane
C
Eder
Andreas
A
Roller
Frank
F
Dicker
Christoph
C
Schmid
Clemens-Martin
CM
Wendtner
Peter
P
Staib
Hubert
H
Serve
Karl-Anton
KA
Kreuzer
Wolfgang
W
Kern
Torsten
T
Haferlach
Claudia
C
Haferlach
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D000090243:Nucleophosmin