Percentage of Aberrant Plasma Cells in the Bone Marrow Plasma Cell Compartment by Flow Cytometry: Correlation with Genetic Changes Involved in Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS)
Brian Kwok, Aine Yung, Prashanti Reddy, Riem Badr, Bashar Dabbas, Yin Xu. Genoptix Medical Laboratory, Carlsbad, CA
Background: The presence of ≥95% aberrant plasma cells in the bone marrow plasma cell compartment (aPC/BMPC) by flow cytometry has previously been shown to predict the risk of progression in patients with monoclonal gammopathy of undetermined significance (MGUS). It is currently thought that progression of MGUS involves sequential accumulation of genetic changes. Primary genetic changes such as hyperdiploidy and IgH translocations occur early, while secondary genetic changes such as deletion of 17p, deletion of chromosome 13, and abnormalities of chromosome 1 tend to occur later and are associated with progression. In this study, we examine the possible correlation between the aPC/BMPC by flow cytometry with various genetic changes in MGUS.
Design: Bone marrow aspirates from 50 patients with MGUS were analyzed by flow cytometry. Absence of CD19 or CD45, and expression of CD56 were used for the identification of aberrant plasma cell phenotypes. FISH analysis utilizing probes for 1p/1q, 5p/5q, 13q, 17p, t(4;14), t(11;14), and t(14;16) was concurrently performed on the bone marrow aspirates after plasma cell enrichment with anti-CD138 magnetic beads.
Results: Among the 50 patients with MGUS, the aPC/BMPC ranged from 32% to 98%. Primary genetic changes were detected in 72% of the patients, and secondary genetic changes in 22%. 11 (22%) of the 50 patients with MGUS had ≥95% aPC/BMPC, while 39 (78%) had <95% aPC/BMPC. Patients with ≥95% aPC/BMPC had higher frequency of both primary and secondary genetic changes than patients with <95% aPC/BMPC, with the exception of t(11;14). Deletion of 17p was not observed in any of the 50 patients with MGUS.
|≥95% aPC/BMPC (n=11)||<95% aPC/BMPC (n=39)|
|Primary genetic changes||91%||67%|
|Secondary genetic changes||36%||18%|
|Deletion of 17p||0%||0%|
|Deletion of chromosome 13||33%||15%|
|Abnormalities of chromosome 1||9%||3%|