Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes

Abstract

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) includes heterogeneous conditions such as previous history and specific cytogenetic and morphological properties. In this study, we analyze genetic aberrations using an RNA-based next-generation sequencing (NGS) panel assay in 45 patients with AML-MRC and detect 4 gene fusions of KMT2A-SEPT9, KMT2A-ELL, NUP98-NSD1, and RUNX1-USP42 and 81 somatic mutations. Overall, all patients had genetic aberrations comprising of not only cytogenetic changes, but also gene fusions and mutations. We also demonstrated several characteristic genetic mutations according to the AML-MRC subgroup. TP53 was the most commonly mutated gene (n = 11, 24%) and all were found in the AML-MRC subgroup with myelodysplastic syndrome-defining cytogenetic abnormalities (AML-MRC-C) (p = 0.002). These patients showed extremely poor overall survival not only in AML-MRC, but also within the AML-MRC-C subgroup. The ASXL1 (n = 9, 20%) and SRSF2 (n = 7, 16%) mutations were associated with the AML-MRC subgroup with >50% dysplasia in at least two lineages (AML-MRC-M) and were frequently co-mutated (55%, 6/11, p < 0.001). Both mutations could be used as surrogate markers to diagnose AML-MRC, especially when the assessment of multilineage dysplasia was difficult. IDH1/IDH2 (n = 13, 29%) were most commonly mutated in AML-MRC, followed by CEBPA (n = 5, 11%), PTPN11 (n = 5, 11%), FLT3 (n = 4, 9%), IDH1 (n = 4, 9%), and RUNX1 (n = 4, 9%). These mutations were not limited in any AML-MRC subgroup and could have more significance as a risk factor or susceptibility marker for target therapy in not only AML-MRC, but also other AML categories.

Clinical Outcomes of Acute Myeloid Leukemia Patients Harboring the RUNX1 Mutation: Is It Still an Unfavorable Prognosis? A Cohort Study and Meta-Analysis

“…The 225 remaining articles underwent full-length article reviews. In total, 24 studies were eventually included in our meta-analysis: 12 prospective studies [ 9 , 13 , 14 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], 11 retrospective studies [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]), and our prospective cohort study. Supplementary Data S5 illustrates the literature review and article selection process.…”

Perspectives on acute myeloid leukemia diagnosis: a comparative analysis of the latest World Health Organization and the International Consensus Classifications

“…The majority of cases were originally classified as AML-MRC according to WHO2016, while 8.2% were reclassified from ‘AML with RUNX1 mutation’ and 15.2% from AML-NOS. The redefined AML-MR appears to provide a clear and simplified diagnostic approach as it removes morphology alone as a diagnostic criterion [ 7 , 8 ]. Further, the AML-MR patients exhibited significantly worse survival outcomes compared to AML-Diff patients.…”

FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer

“…In RT-PCR, POLR2A and ACTB were used to normalize expression, while the NGS panel contained CHMP2A, GPI, RAB7A, and VCP. Thus far, use of the relative gene expression data obtained with the applied NGS panel for genetic profiling has been described for acute myeloid leukemia [40], while it was previously limited to determining gene fusion occurrence [41,42].…”