Abstract
Introduction: Myeloid sarcoma (MS) is a rare hematological neoplasm whose knowledge is largely based on case reports. Whether MS can be divided into different risk group as acute myeloid leukemia (AML) is an issue of concern. Molecular testing with high sensitivity may be of great help in diagnosis and outcome prediction. This study analyzed the clinical features, outcome, cytogenetical and molecular characteristics of MS patients in West China hospital of Sichuan University, China between 2006 and 2016.
Method and result: Thirty-one cases of MS with clinical data available were analyzed in this study. Among them, 8 tumor samples (5 formalin-fix paraffin-embedded tissue and 3 bone marrow tissue) were appropriate for RNA-seq (NGS). The average age at diagnosis MS was 35.2±13.2 years (range 8-61). The mean follow-up period was 32 months (range 1-58). The most common molecular abnormality was FLT3-ITD (29, 4/14) and AML1-ETO fusion (21%). Eighteen patients (58%) presented as de novo MS, 9 patients had simultaneous AML, 3 patients had other hematological neoplasms. Within 18 de novo MS patients, 7 had progressed to AML in 2 to 42 months, the mean progression time was 18.7±17.7 months. The overall survival of this series was range from 2 to 58+ months, 2-year survival rates was 75.8%. Sixty-six fusion transcripts were identified by RNA-seq, including one recurrent transcript: CBFβ/MYH11. Involved genes included a number of hematologic or solid tumor associated genes. Functional annotation of fusion transcripts revealed these fusion genes might involve hematopoiesis, apoptosis, telomere stability, core binding factor, ubiquitination, transmethylation, etc.
Conclusion and discussion: The prognosis of MS patients was heterogeneous and the prognostic genetic markers were similar to AML. Clinical application of NGS-based RNQ-seq profiling in tumor sample is reliable and feasible. FLT3-ITD and AML1-ETO were the most common molecular abnormalities in MS. RNA-seq could identify fusion genes and prognosis associated gene mutation in MS, thus could help to diagnose, predict prognosis and guide therapy, especially in isolated MS, or MS with trace bone marrow involvement. RNA-seq based molecular profiling of MS needs to be further elucidated in the pathogenesis of MS and in the risk stratification of MS patients.
No relevant conflicts of interest to declare.
