AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: Prognostic implication and interaction with other gene alterations
Journal
Blood
Journal Volume
114
Journal Issue
26
Pages
5352-5361
Date Issued
2009
Author(s)
Liu C.-Y.
Tseng M.-H.
Huang C.-F.
Lee F.-Y.
Liu M.-C.
Abstract
Somatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in Nterminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML. ? 2009 by The American Society of Hematology.
Other Subjects
anthracycline; CD15 antigen; CD19 antigen; CD33 antigen; CD34 antigen; CD56 antigen; cytarabine; HLA DR antigen; idarubicin; lactate dehydrogenase; mitoxantrone; mixed lineage leukemia protein; nucleophosmin; transcription factor RUNX1; transcription factor RUNX1; acute granulocytic leukemia; adolescent; adult; aged; allogeneic hematopoietic stem cell transplantation; amino terminal sequence; antigen expression; article; carboxy terminal sequence; chromosome aberration; clinical feature; controlled study; disease course; drug megadose; female; gene mutation; human; immunophenotyping; laboratory test; leukemia cell; major clinical study; male; multiple cycle treatment; priority journal; prognosis; sequential analysis; acute granulocytic leukemia; amino acid sequence; disease free survival; genetics; Kaplan Meier method; middle aged; molecular genetics; mortality; mutation; nucleotide sequence; risk factor; sex difference; Amino Acid Sequence; Base Sequence; Core Binding Factor Alpha 2 Subunit; Disease-Free Survival; DNA Mutational Analysis; Female; Humans; Immunophenotyping; Kaplan-Meiers Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Molecular Sequence Data; Mutation; Prognosis; Risk Factors; Sex Factors
Type
journal article