Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method.
Surbhi SidanaDragan JevremovicRhett P KetterlingNidhi TandonAngela DispenzieriMorie A GertzPatricia T GreippLinda B BaughnFrancis K BuadiMartha Q LacyWilliam MoriceCurtis HansonMichael TimmDavid DingliSuzanne R HaymanWilson I GonsalvesPrashant KapoorRobert A KyleNelson R LeungRonald S GoJohn A LustSundararajan Vincent RajkumarShaji K KumarPublished in: American journal of hematology (2019)
Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.
Keyphrases
- newly diagnosed
- flow cytometry
- end stage renal disease
- ejection fraction
- single molecule
- copy number
- chronic kidney disease
- prognostic factors
- free survival
- multiple myeloma
- peritoneal dialysis
- circulating tumor
- single cell
- cell free
- healthcare
- gene expression
- dna methylation
- bone marrow
- oxidative stress
- mitochondrial dna
- mesenchymal stem cells
- health information
- signaling pathway
- quantum dots
- endoplasmic reticulum stress
- fluorescent probe
- fluorescence imaging