Contributions
Abstract: PB1926
Type: Publication Only
Background
Recent findings indicate that vitamin D (VD) might impact hypomethylating therapy of myelodysplastic syndromes (MDS). Epigenetic activity of VD is mainly mediated through interaction with its nuclear receptor (VDR). Activated VDR binds to specific genomic sequences (VD response elements) which influence gene transcription by histone modification, mainly acetylation but also demethylation. Among genes affected by VD/VDR is BGLAP encoding for the non-collagenous protein osteocalcin (OCN) produced by osteoblasts and implicated in osteogenesis. Furthermore, it has been shown that OCN is expressed by activated hematopoietic stem cells in hematological malignancies.
Aims
We initiated an exploratory study, collecting patients' data on serum VD, and osteocalcin (OCN)-levels in 59 unselected patients with MDS, MDS/myeloproliferative neoplasm (MPN) and secondary acute myeloid leukemia (sAML).
Methods
Serum VD levels were assessed by measuring 25-hydroxyvitamin D (25(OH)D), the biochemical indicator of VD status. Analysis was done by chemiluminescence immunoassay. Intact OCN is unstable due to protease cleavage between amino acids 43 and 44. The N-MID-fragment, resulting from cleavage, is considerably more stable. Measurement of both intact OCN and the stable N-MID-fragment was effectuated by electrochemiluminescence immunoassay.
Results
We found median serum 25(OH)D levels (normal range 30-100 ng/ml) of 16 ng/ml (RA, RARS, n=35), 23 ng/ml (RAEB-1/2, sAML, n=16), and 20 ng/ml (MDS/MPN, n=8) (p=0.273).When classified by IPSS-R, median serum 25(OH)D levels were 18 ng/ml in '(very) low' (n=20), 16.5 ng/ml in 'intermediate' (n=14), and 29.5 ng/ml in '(very) high' (n=6) with p=0.102.Regarding cytogenetic risk classification median serum 25(OH)D levels were 18 ng/ml in '(very) good' (n=48), 19 ng/ml in 'intermediate' (n=8), and 18.5 ng/ml in '(very) poor' (n=4) cytogenetic risk patients (p=0.738).Median serum OCN levels (normal range 11-46 ng/ml) were 19 ng/ml (RA, RARS, n=33) and 16.2 ng/ml (higher-risk MDS/sAML, n=16), (p=0.136). IPSS-R risk classification resulted in median serum OCN levels of 17.4 ng/ml in IPSS-R '(very) low' (n=17), 16.2 ng/ml in 'intermediate' (n=15), and 21.7 ng/ml in '(very) high' (n=6), (p=0.701). Cytogenetic risk classification had no impact on median serum OCN levels (p=0.271).
Conclusion
In summary, our cohort of patients with MDS, MDS/MPN and sAML show clearly decreased serum VD levels. The preliminary results suggest a tendency of serum VD levels to increase with higher risk MDS/sAML which is supported by positive Kendall's tau (0.210). Serum OCN levels lie below normal limits, but seem not to be affected by disease risk. These results suggest specific hypotheses regarding the pathomechanism that shall be investigated on an enlarged data set, which we are continuously collecting.
Session topic: 10. Myelodysplastic syndromes - Clinical
Keyword(s): MDS/AML
Abstract: PB1926
Type: Publication Only
Background
Recent findings indicate that vitamin D (VD) might impact hypomethylating therapy of myelodysplastic syndromes (MDS). Epigenetic activity of VD is mainly mediated through interaction with its nuclear receptor (VDR). Activated VDR binds to specific genomic sequences (VD response elements) which influence gene transcription by histone modification, mainly acetylation but also demethylation. Among genes affected by VD/VDR is BGLAP encoding for the non-collagenous protein osteocalcin (OCN) produced by osteoblasts and implicated in osteogenesis. Furthermore, it has been shown that OCN is expressed by activated hematopoietic stem cells in hematological malignancies.
Aims
We initiated an exploratory study, collecting patients' data on serum VD, and osteocalcin (OCN)-levels in 59 unselected patients with MDS, MDS/myeloproliferative neoplasm (MPN) and secondary acute myeloid leukemia (sAML).
Methods
Serum VD levels were assessed by measuring 25-hydroxyvitamin D (25(OH)D), the biochemical indicator of VD status. Analysis was done by chemiluminescence immunoassay. Intact OCN is unstable due to protease cleavage between amino acids 43 and 44. The N-MID-fragment, resulting from cleavage, is considerably more stable. Measurement of both intact OCN and the stable N-MID-fragment was effectuated by electrochemiluminescence immunoassay.
Results
We found median serum 25(OH)D levels (normal range 30-100 ng/ml) of 16 ng/ml (RA, RARS, n=35), 23 ng/ml (RAEB-1/2, sAML, n=16), and 20 ng/ml (MDS/MPN, n=8) (p=0.273).When classified by IPSS-R, median serum 25(OH)D levels were 18 ng/ml in '(very) low' (n=20), 16.5 ng/ml in 'intermediate' (n=14), and 29.5 ng/ml in '(very) high' (n=6) with p=0.102.Regarding cytogenetic risk classification median serum 25(OH)D levels were 18 ng/ml in '(very) good' (n=48), 19 ng/ml in 'intermediate' (n=8), and 18.5 ng/ml in '(very) poor' (n=4) cytogenetic risk patients (p=0.738).Median serum OCN levels (normal range 11-46 ng/ml) were 19 ng/ml (RA, RARS, n=33) and 16.2 ng/ml (higher-risk MDS/sAML, n=16), (p=0.136). IPSS-R risk classification resulted in median serum OCN levels of 17.4 ng/ml in IPSS-R '(very) low' (n=17), 16.2 ng/ml in 'intermediate' (n=15), and 21.7 ng/ml in '(very) high' (n=6), (p=0.701). Cytogenetic risk classification had no impact on median serum OCN levels (p=0.271).
Conclusion
In summary, our cohort of patients with MDS, MDS/MPN and sAML show clearly decreased serum VD levels. The preliminary results suggest a tendency of serum VD levels to increase with higher risk MDS/sAML which is supported by positive Kendall's tau (0.210). Serum OCN levels lie below normal limits, but seem not to be affected by disease risk. These results suggest specific hypotheses regarding the pathomechanism that shall be investigated on an enlarged data set, which we are continuously collecting.
Session topic: 10. Myelodysplastic syndromes - Clinical
Keyword(s): MDS/AML