Clinical and experimental Medicine
Contributions
Type: Publication Only
Background
The RPS14 gene, located on chromosome 5 and involved in the ribosomal protein synthesis, has been reported as a causal factor in the 5q- syndrome, where its up-regulation during treatment with lenalidomide has been associated with best responses. RPS14 expression in non-5q-MDS was reported in 53%>71% of cases. Interestingly, in low and intermediate-1 IPSS subgroups, patients with lower RPS14 expression had longer OS.
Aims
The aim of this study was to assess the RPS14 expression in a larger series of non-5q- MDS patients.
Methods
A total of 112 patients, 45% females and 55% males, with a median age of 71-year (range 19-89), were enrolled in 5 different Italian institutions from March 2010 to October 2014. Nine patients were affected by CMMoL; the prognosis of the remaining 103 cases was determined according to the IPSS in low (36%), intermediate-1 (31%), intermediate-2 (21%), and high risk (12%). About 40% of cases were affected by RCMD, 24% by RAEB-2, and 13% by RA. Twelve bone marrow samples from healthy donors have been used as normal references.
Results
In healthy donors, the mean RPS14 expression was 0.94±0.26; in the whole MDS series, it was 0.57±0.42. In comparison with healthy controls, the 52% of MDS cases showed lower RPS14 expression levels: 79% in the RA, 56% in the RAEB1, 44% in the RAEB-2, and 41% in the RCMD subgroups.
When patients were stratified according to the IPSS, in the half of the low, intermediate-1 and intermediate-2 cases RPS14 was under-expressed, opposite to one third of the high risk and 13% of the CMMoL patients only.
No relationships with age or sex were observed.
To evaluate if the haploinsufficiency would be responsible of the low expression of RPS14 gene, we performed the copy number assay on 32 MDS, 15 healthy donors, and 3 patients with 5q- syndrome: in 91% of cases the copy number assay excluded the haploinsufficiency.
Summary
Our study showed in a large series of patients that a lower RPS14 expression interests the half of the non-5q- cases, especially those affected by RA and at low and intermediate IPSS risk. Other authors previously reported that low expression of RPS14 was not due to promoter hypermethylation. Here we demonstrated that also the haploinsufficience is not the cause of the RPS14 low expression. Moreover, our findings suggest a possible role for lenalidomide in non-5q- MDS, especially in low risk patients.
Keyword(s): Myelodysplasia, RPS19
Session topic: Publication Only
Type: Publication Only
Background
The RPS14 gene, located on chromosome 5 and involved in the ribosomal protein synthesis, has been reported as a causal factor in the 5q- syndrome, where its up-regulation during treatment with lenalidomide has been associated with best responses. RPS14 expression in non-5q-MDS was reported in 53%>71% of cases. Interestingly, in low and intermediate-1 IPSS subgroups, patients with lower RPS14 expression had longer OS.
Aims
The aim of this study was to assess the RPS14 expression in a larger series of non-5q- MDS patients.
Methods
A total of 112 patients, 45% females and 55% males, with a median age of 71-year (range 19-89), were enrolled in 5 different Italian institutions from March 2010 to October 2014. Nine patients were affected by CMMoL; the prognosis of the remaining 103 cases was determined according to the IPSS in low (36%), intermediate-1 (31%), intermediate-2 (21%), and high risk (12%). About 40% of cases were affected by RCMD, 24% by RAEB-2, and 13% by RA. Twelve bone marrow samples from healthy donors have been used as normal references.
Results
In healthy donors, the mean RPS14 expression was 0.94±0.26; in the whole MDS series, it was 0.57±0.42. In comparison with healthy controls, the 52% of MDS cases showed lower RPS14 expression levels: 79% in the RA, 56% in the RAEB1, 44% in the RAEB-2, and 41% in the RCMD subgroups.
When patients were stratified according to the IPSS, in the half of the low, intermediate-1 and intermediate-2 cases RPS14 was under-expressed, opposite to one third of the high risk and 13% of the CMMoL patients only.
No relationships with age or sex were observed.
To evaluate if the haploinsufficiency would be responsible of the low expression of RPS14 gene, we performed the copy number assay on 32 MDS, 15 healthy donors, and 3 patients with 5q- syndrome: in 91% of cases the copy number assay excluded the haploinsufficiency.
Summary
Our study showed in a large series of patients that a lower RPS14 expression interests the half of the non-5q- cases, especially those affected by RA and at low and intermediate IPSS risk. Other authors previously reported that low expression of RPS14 was not due to promoter hypermethylation. Here we demonstrated that also the haploinsufficience is not the cause of the RPS14 low expression. Moreover, our findings suggest a possible role for lenalidomide in non-5q- MDS, especially in low risk patients.
Keyword(s): Myelodysplasia, RPS19
Session topic: Publication Only