Genomic profiling in amyloid light-chain amyloidosis reveals mutation profiles associated with overall survival.

Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes.Results: Four recurrent mutations were identified by TGS and verified by Sanger sequencing: ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS.Conclusions: In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.

Preparation of heparin-immobilized PVA and its adsorption for low-density lipoprotein from hyperlipemia plasma.

In this study, heparin was covalently coupled by glutaraldehyde to Poly(vinyl alcohol) [PVA] in solid-liquid two-phase reaction system by two-step synthesis method to prepare a LDL-selective adsorbent. The parameters (the material ratio, reaction time and dosage of catalyzer) were investigated to evaluate their effect upon the immobilized amount of heparin onto the surface of PVA, IR was used to verify the covalent immobilization result and the heparin-modified PVA was also undergone the evaluation of its adsorption capability for low-density lipoprotein from hyperlipemia plasma, and its hemocompatibility was preliminarily evaluated by platelet adhesion test. Results showed: (1) under optimized reaction conditions the highest immobilization amount of heparin onto PVA surface within the experiments of this study has been obtained; (2) the optimized reaction conditions were: (i) at the refluxing temperature 78 degrees C; (ii) the material ratio of "PVA(g): 50% glutaraldehyde (ml)" was about "1:3"; (iii) the reaction time was about 5 h; and (iv) the amount of catalyzer (concentrated HCL) was about 1% of the 50% glutaraldehyde; (3) within the experiments of this study the highest immobilization amount would be up to 25 microg heparin on the surface of per g PVA granules; (4) the heparin-modified PVA granules showed significant adsorption for LDL under faintly alkaline environment (pH=7.2-9.5) ; (5) The result of platelet adhesion test showed no platelet adhered to its surface. Therefore, immobilization of heparin onto the surface of a support is one approach to prepare a kind of LDL adsorbent for blood purification.