Molecular and Clinicopathologic Characterization of De Novo AML with Isolated Trisomy 4.
Ashish Bains, Gary Lu, Hui Yao, Rajyalakshmi Luthra, L Jeffrey Medeiros, Rachel L Sargent. UT-MD Anderson Cancer Center, Houston, TX
Background: De novo acute myeloid leukemia (AML) with isolated trisomy 4 is rare. Although the molecular and clinicopathologic features of these cases remain poorly characterized, an association with KIT mutations has been documented in isolated case reports. To better characterize this entity, our study identified de novo cases of AML with isolated trisomy 4, and analyzed the clinicopathologic features and the mutational status of genes frequently mutated in AML.
Design: De novo AML cases with isolated trisomy 4 were identified within our database from 1/1997 to 8/2010. Mutational analysis of FLT3 ITD/TKD, NPM1, KIT exon 17, CEBPA, and codons 12, 13 and 61 of KRAS/NRAS was performed on cases with available DNA. Clinicopathologic data for each case was also reviewed.
Results: 14/20,029 (0.07%) cases of de novo AML cases with isolated trisomy 4 were identified. Patients were 20-84 years old (M:F – 9:5, median age – 53 years). Bone marrow blast percentage ranged from 20-93 (median 84). Cases were classified using the 2008 WHO criteria as: AML with minimal differentiation (n=5), AML without maturation (n=4), AML with maturation (n=3), acute myelomonocytic leukemia (n=1), and AML with myelodysplasia-related changes (n=1). Molecular analysis in 11/14 cases showed: 5/11 (45.5%) with FLT3 ITD/TKD mutations, 4/11 (36.3%) with NPM1 mutations, 1/11 (9.1%) with KIT D816V mutation and 1/11 (9.1%) with codon 12 NRAS mutation. Further analysis revealed isolated FLT3 ITD mutations 1/11 (9%), isolated FLT3 D865 mutations in 1/11 (9%), isolated codon 12 NRAS mutations in 1/11 (9%), isolated NPM1 mutations in 1/11 (9%), combined FLT3 ITD and NPM1 mutations in 2/11 (18%) and combined KIT D816V, FLT3 ITD and NPM1 mutations in 1/11 (9%). CEBPA mutations were not identified in any cases. 12/14 (85.7%) patients achieved complete remission (CR). Of the 12 patients achieving CR, 9 relapsed with a median survival time of 14 months, 2 maintained CR (16 and 101 months respectively) and 1 was lost to follow-up after 39 months. 2/14 patients are deceased following induction chemotherapy. Median overall survival time is 28 months.
Conclusions: Our study shows that de novo AML with isolated trisomy 4 is exceedingly rare and is associated with male predominance, a high BM blast count, and an intermediate to poor prognosis. In addition, FLT3 and NPM1 mutations were observed at the same frequency as in normal karyotype AML. In contrast to what might be expected, KIT mutations are not significantly associated with this entity.
Monday, February 28, 2011 1:00 PM
Poster Session II # 193, Monday Afternoon