Interestingly, there was dim CD45 expression in a subset of polyclonal NPCs in 14 of 34 NPC specimens (mean 86% of NPCs CD45 dim, S

Interestingly, there was dim CD45 expression in a subset of polyclonal NPCs in 14 of 34 NPC specimens (mean 86% of NPCs CD45 dim, S.D.:15, range: 63100%). myeloma (SMM) to the symptomatic multiple myeloma (MM) with its high morbidity and diminished quality of life. Although diagnosis is based upon serum M spike, extent of plasma cell (PC) involvement of the BM and presence of end organ damage, flow cytometric (FC) characterization and quantification of abnormal plasma cells (APCs) has been used in the diagnosis, prognostication and monitoring of PCD (15). FC determination of the percentage of total bone marrow PCs that are phenotypically aberrant (% APC) versus the percent of total PCs with a normal immunophenotype (NPC) allows risk stratification of progression of MGUS and SMM patients to overt MM and can be used for prognostication in MM (612). FC studies can also help predict response to autologous stem cell transplantation (1214). All of the FC studies in PCD rely on an accurate differentiation of APC from NPC. FC analysis provides a consistent and stringent method for differentiating APCs from their normal counterpart based on the expression of a variety of surface antigens and demonstration of intracellular light chain restriction. Aberrant surface antigen expression can be demonstrated in the majority of MGUS, SMM and MM cases, with typical aberrant antigen profiles including expression of CD56, CD20 or CD117, diminished CD38, and complete absence of CD19 and/or CD45 (6,15,16). The simultaneous analysis of CD38, CD56, CD19, CD45 and CD138 expression has been reported to detect a significant APC population in most patients with myeloma, even in the absence of intracytoplasmic immunoglobulin detection (4,5,1517). The precise enumeration of APCs in the presence of NPCs, however, remains challenging, especially in specimens Linaclotide with low numbers of PCs (e.g. MGUS). Panels with greater specificity for differentiating APCs from NPCs are needed to be able to accurately assess prognosis and minimal residual disease. CD81 is strongly expressed on the surface of NPCs but MM cell lines are shown to underexpress CD81, making it a potentially useful marker in differentiating APCs from NPCs (18). Furthermore, levels of CD81 expression may correlate with prognosis in myeloma (19). However, little information is available regarding its expression in the APCs of MM, SMM and MGUS patients. Linaclotide In the current study we evaluated the expression of CD19, CD20, CD38, Linaclotide CD45, CD56, CD81 and CD138 as well as intracellular immunoglobulin light chain (kappa/lambda) in APCs and NPCs in patients with MM, SMM and MGUS to determine their sensitivity and specificity in detecting PCD. Furthermore, we evaluated the role of these markers in an attempt to differentiate the early stage disease of MGUS from SMM and MM. == Materials and Methods == == Patients == Bone marrow aspirates from 59 untreated patients with PCD (14 MGUS, 35 SMM, and 10 MM) were submitted for diagnostic FC evaluation as part of screening for a prospective clinical natural history study (NCT01109407) of myeloma precursor disease and in some cases to determine eligibility for several research protocols. In addition bone marrow was evaluated in 5 patients referred to our institution to rule out MGUS, primarily due to anemia and reported mildly increased Rabbit Polyclonal to VIPR1 plasma cells in bone marrow evaluations performed at other institutions. These 5 patients were determined to have no evidence of a PCD (including absence of M spike, less than 5% PC on BM biopsy, polyclonal PCs by IHC and FC) or other neoplastic process and normal bone marrow specimen. All patients signed institutional review board.