Dysregulation of miRNAs in AL amyloidosis.

Dysregulation of miRNAs in AL amyloidosis.
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DOI:
10.3109/13506129.2011.588977
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发表时间:
2011-09
期刊:
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
影响因子:
--
通讯作者:
Seldin DC
Seldin DC
中科院分区:
其他
文献类型:
--
作者:
Weng L;Spencer BH;SoohHoo PT;Connors LH;O'Hara CJ;Seldin DC

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Bone marrow plasma cells (BMPCs) were purified using anti-CD138 immunomagnetic beads, from aspirates obtained with permission of the Boston University Medical Campus Institutional Review Board, from patients with immunoglobulin light chain (AL) amyloidosis and from controls. Expression levels of MicroRNAs (miRNAs) were compared by microarray; 10 were found to be increased more than 1.5-fold. These results were confirmed using stem-loop RT-qPCR for the most highly upregulated miRNAs, miR-148a, miR-26a, and miR-16. miR-16, a micro-RNA linked to other hematopoietic diseases, was significantly increased in the AL group at diagnosis, and also in treated patients with persistent monoclonal plasma cells in the bone marrow, but not in patients who achieved a hematologic remission after therapy. miR-16 can be derived from the miR-16-1/mirR-15, a cluster on chromosome 13 or the miR-16-2/miR-15b cluster on chromosome 3. The expression of miR-15b was much higher than miR-15a in both AL and control BMPC, suggesting that miR-16 in plasma cells is mainly derived from miR-16-2/miR-15b. The anti-apoptosis gene BCL-2, a putative target mRNA that can be downregulated by miR-16, was expressed in BMPCs from AL patients, despite elevated levels of miR-16. Our data suggests that miRNAs are dysregulated in clonal plasma cells in AL amyloidosis and may be potentially useful as biomarkers of disease.
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期刊: SCIENCE
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