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Acute Myeloid Leukemia with Myelodysplasia-Related Changes with or without Prior Myelodysplastic Syndrome Show Distinct Gene Mutation Profile.
Poster Title: Acute Myeloid Leukemia with Myelodysplasia-Related Changes with or without Prior Myelodysplastic Syndrome Show Distinct Gene Mutation Profile.
Submitted on 08 Feb 2018
Author(s): Mary-Margaret Allen, Mohammad Hussaini, Eric Padron, Hailing Zhang, Xiaohui Zhang, Lynn Moscinski, Ling Zhang, Jinming Song
Affiliations: Moffitt Cancer Center
This poster was presented at USF Health Research Day 2018
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Abstract: Background: Acute myeloid leukemia with myelodysplastic related changes (AML-MRC) usually has a dismal clinical outcome. Within this WHO classification, there are two groups, patients with prior myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN) that progress to AML (hxAML-MRC) and patients that present with de novo AML-MRC (dnAML-MRC) . Lindsley et al. (2015) indicated gene mutations highly specific to secondary AML including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR or STAG2. However, study of differences in gene profiles and clinical outcomes between the two subgroups of AML-MRC is limited. This study seeks to study the subgroups for potential differences. Design: Retrospectively, 398 patients with AML-MRC from 2012-2017 and their Next-Generation Sequencing data were reviewed. We compared mutation profiles and overall survival (OS) of patients with hxAML-MRC to those patients with dnAML-MRC. Patients with a prior history of MDS/MPN were excluded. Results: 180 patients had hxAML-MRC (median age 71 years, male to female ratio (M:F) of 2.28) and 218 patients presented with dnAML-MRC (median age 66 years, M:F of 1.38). Patients with prior MDS had a higher average number of mutations (2.62 vs 1.98, p-value = 0.0002). They also had significantly more mutations in ASXL1 (25.56% vs 16.13%, p=0.0242), RUNX1 (22.67% vs 10.00%, p=0.001), SETBP1 (8.93% vs 2.59%, p=0.0105), SRSF2 (20.83% vs 7.77%, p=0.0004), TET2 (23.30% vs 14.08%, p=0.0246), and U2AF1 (13.10% vs 5.18%, p=0.0094) than dnAML-MRC. There was no significant difference between the two groups in frequencies of mutations in ABL1, CBL, CEBPA, CSF3R, CUX1, DNMT3A, ETV6, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KMT2A, KRAS, MPL, MYD88, NPM1, NRAS, PHF6, SF3B1, SH2B3, TP53, or ZRSR2. The dnAML-MRC appeared to show more mutations in the WT1 gene (6.79% vs 1.94%, p=0.0528), although statistically insignificant. Despite the distinct mutation profile, the median OS between the two groups was similar (10 months hxAML-MRC vs 12 months dnAML-MRC, p= >0.05). Conclusions: Similar to the Lindsley et al. report, we showed the patients with hxAML-MRC have a greater number of mutated genes and significantly more mutations in SRSF2, U2AF1, TET2, ASXL1, RUNX1 and SETBP1. These findings suggest that patients with and without prior MDS are distinct subsets of AML-MRC, which may require different target therapy in the era of personalized medicine.Summary: AML-MRC can occur following a previously diagnosed MDS or as de novo AML. Here, NGS molecular data is analyzed to see if there were differences in the genetic profiles between the two subgroups.References: Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, Damon LE, Powell BL, Lindeman N, Steensma DP, Wadleigh M, DeAngelo DJ, Neuberg D, Stone RM, Ebert BL. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015 Feb 26;125(9):1367-76.
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