High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1 T1: frequency and impact on clinical outcome

作者：Krauth M T; Eder C; Alpermann T; Bacher U; Nadarajah N; Kern W; Haferlach C; Haferlach T; Schnittger S^*

来源：Leukemia, 2014, 28(7): 1449-1458.

DOI：10.1038/leu.2014.4

• acute myeloid leukemia
• t(8
• 21)/RUNX1-RUNX1T1
• secondary mutations
• KIT mutation
• ASXL1 mutation
• prognosis

t(8;21)/RUNX1-RUNX1T1-positive acute myeloid leukemia (AML) is prognostically favorable; however, outcome is heterogeneous. We analyzed 139 patients with t(8;21)/RUNX1-RUNX1T1-positive AML (de novo: n = 117; therapy-related: n = 22) to determine frequency and prognostic impact of additional genetic abnormalities. All patients were investigated for mutations (mut) in ASXL1, FLT3, KIT, NPM1, MLL, IDH1, IDH2, KRAS, NRAS, CBL and JAK2. Sixty-nine of 139 cases (49.6%) had 1 mutation in addition to RUNX1-RUNX1T1, and 23/139 (16.5%) had >= 2 additional mutations. Most common were KITmut (23/139; 16.5%), NRASmut (18/139; 12.9%) and ASXL1mut (16/139; 11.5%). FLT3-ITD, FLT3-TKDmut, CBLmut, KRASmut, IDH2mut and JAK2mut were found in 2.9-5.0%. Additional chromosomal abnormalities (ACAs) were found in 97/139 (69.8%). Two-year overall survival (OS) was 73.4% in 111 intensively treated patients. KITD816mut negatively impacted on OS in de novo AML (2-year OS: 59.1% vs 82.0%, P = 0.03), ASXL1mut on EFS (de novo AML: 20% vs 59.1%, P = 0.011; total cohort: 28.6% vs 56.7%, P = 0.021). Sex chromosome loss was favorable (2-year EFS: 66.9% vs 43.0%, P = 0.031), whereas +8 was adverse on EFS (2-year EFS: 26.7% vs 55.9%, P = 0.02). In conclusion, t(8;21)/RUNX1-RUNX1T1-positive AML shows a high frequency of additional genetic alterations. Investigation for KITD816 and ASXL1mut combined with investigation of ACAs is recommended in t(8;21)/RUNX1-RUNX1T1-positive AML because of the prognostic significance of these parameters.

• 出版日期2014-7