Monitoring treatment or progression of myeloma

A multiple myeloma, bone marrow technology, applied in the field of monitoring the treatment or progress of myeloma, can solve problems such as genetic information interference

Inactive Publication Date: 2018-09-28
阿尔佛雷德医疗集团
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current practice for diagnosis and prognostic prediction is to perform serial BM biopsies, but the genetic information (GI) obtained from the biopsies is confounded by known interclonal and intraclonal heterogeneity of one or more tumors

Method used

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  • Monitoring treatment or progression of myeloma
  • Monitoring treatment or progression of myeloma
  • Monitoring treatment or progression of myeloma

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0242] Peripheral blood (PB) collection and processing:

[0243] PB samples (30ml) were obtained from normal volunteers (NV) or MM patients using 10ml Streck Cell-Free DNA BCT tubes or 10ml EDTA tubes after obtaining informed consent according to the Alfred Human Ethics Committee . Immediately after sample collection, the tubes were inverted to mix the blood with the preservative in the collection tube, which prevents the release of DNA from blood cells during sample processing and storage (Das K et al. (2014) Molecular diagnosis & therapy 18 (6): 647-653; Qin J, Williams TL and Fernando MR (2013) BMC research notes [BMC research notes] 6: 380). Plasma (PL) was separated from PB by centrifugation at 820 xg for 10 minutes (min). The supernatant was collected without disturbing the cell layer and centrifuged again at 16,000 xg for 10 min to remove any remaining cell debris. Supernatants were collected and stored in 1 ml aliquots at −80 °C for long-term storage until isolati...

example 2

[0280] Cell-free DNA content is significantly higher in MM patients than in normal volunteers

[0281] The amount of cfDNA in MM patients (n=37) and NV (n=21) was determined. Higher amounts of cfDNA were obtained from MM patients than from NV (median 23 ng / ml [range 5-195 ng / ml] vs 15 ng / ml [range 6-32 ng / ml], respectively, p=0.0085, figure 1 ). When the amount of cfDNA was correlated with disease stage, it was evident that patients with active disease (ND and recurrent disease) had significantly higher amounts of cfDNA compared to NV (p=0.0067; figure 2 ). Although the amount of cfDNA was significantly higher in patients with active disease, its level did not correlate with the amount of paraprotein, serum free light chains, and BM MM cell ratio ( image 3 , Spearman rank correlation coefficient).

example 3

[0283] Analysis of both BM MM cells and ctDNA provides a comprehensive elucidation of the mutational landscape of MM patients

[0284] Contemporaneous CD138-enriched MM tumor cell populations were collected from 48 MM patients (15 newly diagnosed [ND] patients and 33 relapsed / refractory [RR] patients), and all paired BM MM DNA and ctDNA specimens as well as 6 wild-type (WT) DNA controls underwent OMD. A total of 128 mutations were detected in MM patients (BM and / or ctDNA) (KRAS n=65 [50.7%], NRAS n=37 [28.9%], BRAF n=10 [7.8%], TP53n=16 [12.5%] %]), not detected in WT control ( Figure 4 ). Of the 128 mutations, n=38 mutations were found in both BM and PL, n=59 mutations were found in BM and n=31 mutations were found in PL. Furthermore, a total of 53.9% of mutations were found in PL, indicating the presence of ctDNA in MM. Ten of the 48 patients had 31 mutations in the PL that were not present in the BM, so a total of 24.2% were detected exclusively or predominantly dist...

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Abstract

The present invention relates to methods and kits for diagnosing myeloma, monitoring disease progression or treatment efficacy in an individual having a myeloma. In one aspect, the invention relates to A method for monitoring the response of an individual to treatment for multiple myeloma, the method comprising providing cell-free nucleic acids derived from a sample of peripheral blood from an individual that has undergone treatment for multiple myeloma; assessing the cell-free nucleic acids for a mutation in any one or more nucleotide sequences from a KRAS, NRAS, BRAF and / or TP53 gene; wherein an absence of, or reduction in the number of, mutations in a nucleotide sequence from a KRAS, NRAS, BRAF and / or TP53 gene indicates a response of the individual to treatment for multiple myeloma.

Description

[0001] This application claims priority from Australian provisional applications AU 2015905013 and AU 2016903019, the entire disclosures of which are incorporated herein in their entirety. technical field [0002] The present invention relates to methods and kits for determining whether an individual has myeloma, monitoring the progression of myeloma, or the efficacy of a treatment for myeloma. Background technique [0003] Multiple myeloma (MM) is an incurable hematological malignancy characterized by multifocal tumor deposits throughout the bone marrow (BM). Karyotype instability and abnormal chromosome number are present in almost all MMs. Primary translocations involving immunoglobulin (IgH) genes and FGFR3 / MMSET, CCND1, CCND3, or MAF occur during disease onset, and secondary translocations involving MYC genes occur during disease progression. The treatment of MM has made remarkable progress through the implementation of proteasome inhibitors and immunomodulators, howev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q2600/118C12Q2600/156C12Q1/6886A61P35/00A61P7/00C12Q2600/158C12Q2600/106C12Q2600/112
Inventor A.斯潘塞S.米思拉普拉布
Owner 阿尔佛雷德医疗集团
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