SF3B1 mutations (SF3B1mut) correlate with the presence of ring sideroblasts (RS) and can be found in MDS and in AML.


To evaluate the incidence of SF3B1mut in a large cohort of MDS and AML patients (pts) with ≥15% RS, and furthermore correlate to percentage of blasts, mutation load, concomitant genetic markers and to define their prognostic impact.

Patients and Methods

We investigated bone marrow (BM) in 1,238 newly diagnosed pts with MDS (n=770) and AML (n=468). In all cases MGG, MPO, NSE and iron staining was performed according to WHO criteria. 717 pts showed ≥15% RS and thus were included in this study. In all pts SF3B1mut and cytogenetic analysis was available.


579/717 (80.8%) pts were diagnosed with MDS (93.3% de novo; 6.7% therapy-related), and 138/717 (19.2%) with AML (61.6% de novo, 33.3% secondary, and 5.1% therapy-related). MDS subtypes were distributed as follows: 329 (56.8%) RCMD, 126 (21.8%) RARS, 63 (10.9%) RAEB-1, 55 (9.5%) RAEB-2, and 6 (1.0%) MDS with isolated del(5q). AML FAB subtypes were as follows: 11 (8.0%) M0; 10 (7.2%) M1; 70 (50.7%) M2, 14 (10.1%) M4, and 33 (23.9%) M6.

Mean percentage of RS was 50.4% and differed between MDS and AML (52.9% vs 40.1%; p<0.001). Within the MDS cohort mean RS differed between the MDS WHO categories following an ascending order from MDS with isolated del(5q) (36.8%), RAEB-2 (40.0%), RAEB-1 (45.0%), RCMD (55.3%), to RARS (57.0%). In contrast, no differences were seen within the different AML FAB subtypes (mean RS M0: 40.3%, M1: 37.0%, M2: 40.1%, M6: 44.2%).

Per definition, mean BM blasts differed between MDS and AML (3.6% vs 32.6%; p<0.001). Of note, percentages of RS and BM blasts were negatively correlated in the total cohort (p<0.001; r: -0.253) as well as for the cohort of MDS (p<0.001; r: -0.238) and showed a respective trend within the cohort of AML (p=0.072; r: -0.154). Within the cohort of MDS percentages of RS were higher in SF3B1mut vs wild-type (wt) pts (59.1% vs 42.3%; p<0.001) and mutation load of SF3B1mut (median 37.5%; range 10%-60%) correlated to the amount of RS (p<0.001, r: 0.258). No respective difference or correlation was seen within the AML cohort.

Regarding cytogenetics SF3B1mut were more frequent in pts with normal karyotype than in pts with aberrant karyotype in the MDS cohort (76.1% vs 43.7%; p<0.001) as well as in the AML cohort (48.7% vs 18.2%; p=0.001). Further in the total cohort SF3B1mut were less frequent in ASXL1mut than in ASXL1wt (24.0% vs 48.5%; p=0.041), and within the AML cohort SF3B1mut showed a positive correlation to MLL-PTD (71.4% vs 25.7%; p=0.019). Additionally, we analyzed the position of the SF3B1mut. Within the total cohort 21 different amino acid positions were affected. We focused on the most frequent positions: 700 (55.9%), 666 (16.2%), 662 (8.0%), 625 (7.5%), 622 (4.0%), and 663 (1.7%). Mutations at position 666 were less frequent within MDS than in AML pts (14.3% vs 35.1%; p=0.003) and mutations at amino acid position 662 indicated a trend to be prevalent in MDS only (8.8% vs 0.0%; p=0.059).

In addition, an analysis was performed for the contiguous subcohorts of 69 MDS with BM blasts between 10-19% and 44 AML with 20-29% (formerly RAEB-t). Neither differences in mean percentage of RS (38.7% vs 39.3%; n.s.), frequencies of SF3B1mut (17.4% vs 22.7%; n.s.), nor differences within the position of the mutation were identified.

Follow-up data was available in 304 patients. Within the cohort of MDS SF3B1mut pts had better overall survival (OS) than SF3B1wt pts (5-year-survival rate 72.7% vs 35.2%; p<0.001). This holds true within the subcohort of normal karyotype (75.0% vs 35.6%; p=0.004) and within aberrant karyotype (67.6% vs 39.7%; p=0.012). No respective effect on OS was seen within the AML cohort. Also within the subgroup of early MDS (RCMD, RARS, and MDS with isolated del(5q); n=222) SF3B1mut pts had better OS than SF3B1wt pts (74.9% vs 48.2%; p<0.001), this holds true in patients with normal as well as in patients with aberrant karyotype (77.4% vs 56.1%; p=0.095 and 68.5% vs 44.6%; p=0.042, respectively). In contrast SF3B1 mutation status had no impact on OS within the cohort of MDS with excess of blasts (RAEB-1 and RAEB-2 together n=45).


1) Percentages of RS are decreasing with increasing BM blasts percentages. 2) Different mutations within the SF3B1 gene are correlated to either MDS or AML. 3) The prognostic impact of SF3B1mut was only observed in patients with early MDS, but not in RAEB-1/2 or AML.


Alpermann: MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Author notes


Asterisk with author names denotes non-ASH members.