Liangping Weng

Publications (2)5.78 Total impact

• Article: Immunoglobulin light chain, Blimp-1 and cytochrome P4501B1 peptides as potential vaccines for AL amyloidosis.

  Amanda Flies, Tahamtan Ahmadi, Ashley J Parks, Tatiana Prokaeva, Liangping Weng, Sandra Solomon Rolfe, David C Seldin, David H Sherr
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  ABSTRACT: Amyloid light chain (AL) amyloidosis is a lethal disorder characterized by the pathologic deposition of clonal plasma cell-derived, fibrillogenic immunoglobulin light chains in vital organs. Current chemotherapeutic regimens are problematic in patients with compromised organ function and are not effective for all patients. Here, a platform of computer-based prediction and preclinical mouse modeling was used to begin development of a complementary, immunotherapeutic approach for AL amyloidosis. Three peptide/MHC I-binding algorithms identified immunogenic peptides from three AL plasma cell-associated proteins: (1) amyloidogenic λ6 light chains, (2) CYP1B1, a universal tumor antigen hyper-expressed in AL plasma cells and (3) B lymphocyte-induced maturation protein 1 (Blimp-1), a transcription factor required for plasma cell differentiation. The algorithms correctly predicted HLA-A(*)0201-binding native and heteroclitic peptides. In HLA-A2 transgenic mice, these peptides, given individually or in combination, induced potent CTL which kill peptide-loaded human lymphoma cells and/or lymphoma cells producing target protein. Blimp-1 peptide-immunized mice exhibited a reduced percentage of splenic, lymph node and bone marrow plasma cells and a decrease in the absolute number of splenic plasma cells demonstrating (1) presentation of target peptide by endogenous plasma cells and (2) appropriate CTL homing to lymphoid organs followed by killing of target plasma cells. These studies suggest that AL amyloidosis, with its relatively low tumor cell burden, may be an attractive target for peptide-based multivalent vaccines.
  Immunology and Cell Biology 09/2011; 90(5):528-39. · 3.66 Impact Factor
• Article: Dysregulation of miRNAs in AL amyloidosis.

  Liangping Weng, Brian H Spencer, Pamela T SoohHoo, Lawreen H Connors, Carl J O'Hara, David C Seldin
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  ABSTRACT: 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.
  Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 09/2011; 18(3):128-35. · 2.12 Impact Factor