(F)utility of urine Bence Jones proteins for “routine” screening for plasma cell dyscrasia

Testing urine for Bence Jones Protein (BJP) had been a time old procedure used for screening and monitoring of monoclonal disorders since its description. However, has poor sensitivity and despite advances in diagnostic methods of monoclonal disorders it is being continued to be requested in individuals for evaluation of myeloma or plasma cell disorders. Effective utilization and minimizing untimely or unnecessary investigations is important in the evaluation and management of any medical condition. Though, we are hard-wired during our education with some “trigger” or “peculiar” words that make us jump to actions too quickly, without comprehending the actual problem. Supporting evidence is presented to avoid reflexive use of multiple tests and utilize tests that improve utilization, reduce waste, and uphold the Choosing Wisely principles in providing optimal care to the patients.

The symptom and frequency of the patients with multiple myeloma in osteoporotic vertebral body fracture in the elderly

Background: In an aging society, osteoporotic vertebral fracture will continue to rise. Multiple myeloma is mostly developed in elderly, so there is also a possibility to increase the number of multiple myeloma. Multiple myeloma patients tend to have osteolysis lesion especially in the vertebral, so they are easy to injury vertebral fractures. In the medical care of osteoporotic vertebral fracture, it is not rare that we meet with undiagnosed multiple myeloma, but there are few reports of the symptom and frequency of the patients with multiple myeloma included in osteoporotic vertebral fracture. In multiple myeloma patients, early treatments improve consequence. So early medical examination by orthopaedist is clinically important. The purpose of this study is to investigate the symptom and frequency of the patients with multiple myeloma included in osteoporotic vertebral fracture. Methods: Between April 2016 and March 2017, 145 patients was diagnosed osteoporotic vertebral fracture, among these, the 108 patients was chosen with use of our criteria. Among these 108 patients, we examined blood examinations, Bence Jones proteins in urine, monoclonal protein on serum and numbers of vertebral fracture at the first visit to a doctor. Results: 6.5% (7/108) patients was diagnosed with symptomatic multiple myeloma. The rate between 75 to 84 years old patients was 5.1%, over the 85 years old was 8.2%. In the 7 patients, the mean age was 85, hemoglobin was 7.8g/dL and albumin-globulin ratio was 0.83, that was low value in all 7 patients. Existing vertebral lesion was 6.0 bodies. Conclusions: Multiple bone lesions or early refracture of vertebral is positively suspicious symptom of MM. The measurement of electrophoresis of protein, albumin-globulin ratio is recommended with vertebral lesion in elderly. The MM patients having bone lesion are likely to first visit orthopaedist, so it is necessary to positively considerate this pathophysiology.

Historical perspectives in clinical pathology: Bence Jones protein—early urine chemistry and the impact on modern day diagnostics

This is the third in the series of historical articles dealing with developments in clinical pathology. Bence Jones proteins are immunoglobulin light chains found in excessive quantities in urine in multiple myeloma and are believed to be one of the first tumour markers ever discovered . Dr Henry Bence Jones is credited with the discovery of this protein in 1847 that bears his name and he can also be regarded as the first chemical pathologist/clinical chemist. Since then, numerous advances and refinements have been made in the measurement and detection of urine light chain proteins which have resulted in the current sensitive serum free light chain assays used today.

Update on Risk Stratification Model of Smoldering Multiple Myeloma: A Systematic Review

Background: Smoldering multiple myeloma (SMM) was stratified into risk classes based on several models including Mayo clinic and Spanish myeloma working group models. After the revision of diagnostic criteria for multiple myeloma (MM) in 2014, the ultra-high risk SMM patients (>80% clonal plasma cells at two years) were re-classified as active MM patients. Thus, predictors of progression in patients currently diagnosed as SMM are unknown and reassessment of existing models is required. We aim to identify the risk factors associated with progression in SMM patients classified according to updated guidelines. Methods We performed a literature search following PRISMA guidelines and used following bibliographic databases: MEDLINE (Ovid and PubMed), EMBASE, The Cochrane Library and Cochrane Central Register of Controlled Trials (CENTRAL), as well as annual meetings abstracts from inception till 1st,August 2019. We used MeSH and Emtree terms as well as performed open search for "smoldering multiple myeloma", "smoldering myeloma", and "asymptomatic multiple myeloma". Two independent reviewers screened the literature. We used snowballing technique to screen abstracts and reference within articles to include titles. Cochrane collaboration tool was used to asses risk of bias among included studies Results Our search retrieved 419 titles. After going through the titles and abstracts 38 articles were selected for full text review. Final review led to inclusion of 11 articles. Levels of serum M proteins, percentage of bone marrow plasma cells (BMPCs), serum free light chain ratio (FLCr) and PET/CT scan findings of whole body were most consistently and reliably indicated the progression of SMM to MM (Table 1). New studies are suggesting that B-cell maturation levels (BCMA), evolving M-proteins (eMP) and evolving hemoglobin levels (eHb) are also an accurate measure of SMM progression and should be incorporated in the risk stratification models. A study by Gonsalves WI et al. also suggested that levels of circulating clonal plasma cells with a cutoff of 150 was an important prognostic marker in their study. Immunoparesis status and role of Bence Jones proteins in reliably predicting the progression of SMM was debatable because they were significant in univariate analysis but were not significant in multivariate analysis (Table 1). Conclusion Serum M protein levels (2 g/dL), percentage of BMPCs (20%), serum FLCr (20) and PET/CT scan were reliable in predicting the prognosis of smoldering MM. New techniques like B-cell maturation levels(74.4 ng/mL), evolving M-proteins and evolving hemoglobin levels can play a significant role in proposing future risk predictive models of SMM. Role of immunoparesis and Bence Jones proteins is debatable. Table 1 Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

Effect of Single Amino Acid Substitutions by Asn and Gln on Aggregation Properties of Bence-Jones Protein BIF

The nature of renal amyloidosis involving Bence-Jones proteins in multiple myeloma is still unclear. The development of amyloidosis in neurodegenerative diseases is often associated with a high content of asparagine and glutamine residues in proteins forming amyloid deposits. To estimate the influence of Asn and Gln residues on the aggregation of Bence-Jones protein BIF, we obtained recombinant BIF and its mutants with the substitution of Tyr187→Asn (Y187N) in α-helix of CL domain, Lys170→Asn (K170N) and Ser157→Gln (S157Q) in CL domain loops, Arg109→Asn in VL-CL linker (R109N) and Asp29→Gln in VL domain loop (D29Q). The morphology of protein aggregates was studied at pH corresponding to the conditions in bloodstream (pH 7.2), distal (pH 6.5) and proximal renal tubules (pH 4.5) by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS). The Lys170→Asn replacement almost completely inhibits amyloidogenic activity. The Y187N forms fibril-like aggregates at all pH values. The Arg109→Asn replacement resulted in formation of fibril-like structures at pH 7.2 and 6.5 while the substitutions by Gln provoked formation of those structures only at pH 7.2. Therefore, the amyloidogenic properties are highly dependent on the location of Asn or Gln.