Biology subjects

Kazeroun, M. H.

Publications and source records attributed to Kazeroun, M. H..

2 recordsLinked to original sources

bioRxiv2026

Sequential acquisition of 1p31.1-p12 LOH and 1q Gain is a common double-hit event in relapsed/refractory myeloma

Therapy-driven genomic changes in multiple myeloma (MM) remain poorly defined. We analyzed whole-genome sequencing (WGS) data from relapsed/refractory MM (rrMM, N=386) and identified regional 1p31.1-p12 (hereafter 1pCEN, a region proximal to the centromere) loss-of-heterozygosity (LOH) as the only enriched aberration showing strong therapy-associated clonal selection (clonal timing rank fold-change = 3.7, P<2.2x10-16). This event showed enriched co-occurrence with 1qGain (OR = 2.3 (1.5-3.8), P=2x10-4) forming a recurrent "double-hit" in rrMM. To validate the clonal selection process, we examined three longitudinal cohorts (180 patients, 390 samples) and confirmed clonal expansion of 1pCEN and consistent prevalence of the 1pCEN+1q double-hit (20-24%). Survival analyses demonstrated significantly reduced progression-free survival in rrMM patients with this double-hit compared with those without. Comparison with a large newly diagnosed MM (ndMM) cohort confirmed previously-described 1p32 LOH is the prognostic locus at baseline, whereas 1pCEN is therapy-selected and largely independent of the 1p32 locus. Thus, 1pCEN+1q represents a recurrent double-hit event that clonally emerges in rrMM, conferring selective advantage under drug exposure and is distinct from the ndMM high-risk markers defined by current consensus guidelines. These findings nominate 1pCEN as a new genomic biomarker in rrMM and 1pCEN+1q may help patient stratification for therapeutic monitoring. Key PointsA therapy-driven common genomic double-hit (1p31.1-p12 LOH with 1q gain) clonally emerges in relapsed/refractory myeloma.

cancer biology↗

bioRxiv2026

Early plasma proteomic alterations precede amyloidosis diagnosis, reflecting cardiac and immune dysregulation

Systemic amyloidosis is typically diagnosed only after irreversible organ damage has occurred, limiting the effectiveness of available therapies. Whether the disease is preceded by detectable molecular changes long before clinical presentation has remained unclear. Here, we leveraged population-scale plasma proteomics and longitudinal follow-up from the UK Biobank to investigate early circulating protein signatures associated with future diagnosis of amyloidosis. Among approximately 53,000 participants with proteomic profiling, we identified 61 individuals who developed amyloidosis up to 14 years after protein assessment. Differential expression and correlation analyses identified a seven-protein panel, including MYL3, MYBPC1, NT-proBNP, NPPB, FCRLB, IGFBP1, and FABP1, consistent with early cardiac stress and immune dysregulation. Time-to-event modelling demonstrated robust stratification of amyloidosis risk and timing. Importantly, a parsimonious subset of these proteins retained strong predictive performance, indicating that a reduced set of biologically informative markers is sufficient for risk stratification. Furthermore, these proteomic signals were not explained by pre-existing cardiac disease, clonal haematopoiesis, or related plasma cell disorders, indicating that they capture disease-specific biological processes preceding clinical diagnosis. Together, these findings show that amyloidosis is preceded by persistent plasma proteomic alterations, providing a framework for early risk stratification and insight into the preclinical biology of this under-recognised disease.

bioinformatics↗