Epigenetic inactivation of the hsa-miR-203 in haematological malignancies.
Bottom Line: In CLL, hsa-miR-203 methylation was associated with a higher presenting Hb level (P = 0.033).In conclusion, miR-203, a tumour suppressor gene, was hypermethylated in a tumour-specific manner with gene silencing. hsa-miR-203 was more frequently hypermethylated in lymphoid than myeloid malignancies.In NHL, hsa-miR-203 methylation was associated with concomitant methylation of other tumour suppressor miRNAs.
Affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. email@example.comShow MeSH
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Mentions: Direct sequencing of the M-MSP products from the methylated primary samples showed the expected nucleotide changes after bisulphite treatment, therefore confirming complete bisulphite conversion and specificity of MSP (Fig. 2A). hsa-miR-203 hypermethylation was not detected in any of the CML. On the other hand, hsa-miR-203 methylation was preferentially found in NHL patients with methylation occurring in 1 (5%) ALL, 2 (10%) AML, 21 (42%) CLL and 19 (38.8%) NHL samples (P < 0.0001) (Fig. 2B). hsa-miR-203 was more frequently hypermethylated in lymphoid than myeloid malignancies (P = 0.002). In CLL patients, the mean survival for the whole group was 86.97 months (89.28 months and 76.71 months for those with or without hsa-miR-203 methylation). Moreover, hsa-miR-203 methylation was associated with a higher mean Hb level than the unmethylated patients (12.2 g/dl versus 10.4 g/dl, P = 0.03) but not diagnostic lymphocyte count (P = 0.98) and platelet count (P = 0.55). Moreover, there was no correlation between hsa-miR-203 methylation and age (P = 0.38), gender (P = 0.99), advanced Rai stage (≥stage 2) (P = 0.14), high-risk karyotypic aberrations (P = 0.99) or death (P = 0.76). The projected OS in CLL patients with and without hsa-miR-203 methylation were 69% and 62% (P = 0.76). Amongst lymphoma samples, hsa-miR-203 was methylated in 9 (40.9%) B-cell NHL, 4 (23.5%) T cell and 6 (60%) NK/T cell NHL (P = 0.165). However, hsa-miR-203 methylation did not correlate with age (P = 0.74), gender (P = 0.24), nodal/extranodal presentation (P = 0.383) or Ann Arbor stage (P = 0.118) of the lymphoma patients.
Affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. firstname.lastname@example.org