RNA sequencing of myeloid sarcoma, shed light on myeloid sarcoma stratification

Abstract

Background Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens. Methods Here, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA‐seq) on formalin‐fixed paraffin‐embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities‐based risk stratification using fusion genes and gene mutations. Results A total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1‐RUNX1T1 , CBFβ‐MYH11 , ETV6‐MECOM , FUS‐ERG , and PICALM‐MLLT10 . The prognosis in the adverse‐risk group was significantly worse than that in the favorable/intermediate‐risk group (median survival: 12 months vs. not reached; p = 0.0004). Conclusion These results indicated the efficacy of RNA‐seq using FFPE‐derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.

Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis

“…The KMT2A:: MLLT3 fusion gene was also identified at a pooled prevalence of 19.20% (95% CI -14.60% to 53.00%; I² 79.63%; Figure 3B) (14,43). Furthermore, the CBFB::MYH11 fusion gene was observed at a pooled prevalence of 10.30% (95% CI 5.40% to 15.10%; I² 84.93%; Figure 3C) (9,14,16,24,28,35,38,39,42,45,46,49,50).…”

“…Similarly, the MLL and NPM1 mutations stood out with a prevalence of 17.30% (95% CI -7.40% to 42.0%; I² 98.06%; Figure 2C) (9,22,46) and 17.10% (95% CI 11.60% to 22.60%; I² 93.64%; Figure 2B) (9, 12, 15, 16, 23, 24, 26, 27, 29, 31-37, 39-42, 46), respectively. Additionally, the DNMT3A mutation was observed at a prevalence of 16.10% (95% CI 7.80% to 24.30%; I² 80.7%; Figure 2D) (12,27,28,32,36,40,42,50), while the TET2 mutation had a prevalence of 15.40% (95% CI 12.30% to 18.50%; I² 0%; Figure 2E) (12,15,27,36,40,43,47,49,50). Furthermore, the STAG2 and NRAS mutations exhibited a prevalence of 12.80% (95% CI 0.70% to 24.80%; I² 0%; Figure 2F) (11,15,36) and 11.9% (95% CI 8.10% to 15.70%; I² 39.18%), respectively.…”

“…Figure 3 presents a detailed analysis of the pooled prevalence of fusion genes in patients with MS, highlighting the frequency of various fusion genes within this group. The most predominant fusion gene observed was RUNX1::RUNX1T1, with a remarkable pooled prevalence of 28.10% (95% CI 15.10% to 41.20%; I² 96.39%; Figure 3A) (9,14,25,28,34,35,38,41,42,45,(48)(49)(50). The KMT2A:: MLLT3 fusion gene was also identified at a pooled prevalence of 19.20% (95% CI -14.60% to 53.00%; I² 79.63%; Figure 3B) (14,43).…”

“…Furthermore, we calculated the overall pooled prevalence of AML patients with MS harboring recurrent genetic abnormalities, as per the 2022 World Health Organization classification, to be 36.80% (95% CI: 26.00% to 47.60%; I² 96.85%; Supplementary Data 4) (9, 12, 14-16, 23-29, [31][32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50].…”