62. Characterization of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with KMT2A amplification

Abstract

KMT2A amplification is a rare high risk cytogenetic abnormality in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which has been associated with complex karyotype, resistance to chemotherapy and higher frequency in elderly patients. Comprehensive elucidation of cytogenetic signatures in AML/MDS with KMT2A amplification, the subsequent clinical impact, as well as accompanying gene mutation profile would be beneficial for stratified patient care.

Herein, we present karyotyping/fluorescence in situ hybridization (FISH) data on 42 AML/MDS patients with KMT2A amplification, along with next generation sequencing (NGS) results and prognostic information in a subset of patients. The median age at diagnosis was 70 years. The male to female ratio was 1.8 (27:15). The median survival was 45 days. KMT2A amplification was identified by FISH. Chromosome analysis showed complex karyotype in all cases analyzed (n=38). The structural mechanisms associated with KMT2A amplification included homogeneously staining region (n=27), double minutes (n=6) and ring chromosome 11 (n=8). Deletions of 5q (64%) and 17p (62%) were the most common concurrent cytogenetic findings. Additional major concurrent cytogenetic abnormalities included loss of 7q (31%) and gain of chromosome 8 (29%). NGS results were available for 14 cases and TP53 mutation was the most common alteration (n=12). Other mutations were detected in TET2 (n=2), NSD1 (n=2), SAMD9L (n=2), DNMT3A (n=1), U2AF2 (n=1), FLT3 (TKD, n=1), NOTCH1 (n=1) and SMC3 (n=1).

AML/MDS with KMT2A amplification is associated with poor outcome and specific concurrent cytogenetic and molecular abnormalities. Documenting additional data is valuable for improving the treatment landscape in these myeloid neoplasms.