Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis.
We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM.
CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls.
Patients with AL exhibited an increased cluster of differentiation (CD)19 expression compared with patients with MM, 4.5% (0.1-80.9%) vs. 1.6% (0.1-33.6%; P<0.001) and reduced CD138, with 90.8% (30.4-99.9%) vs. 95.0% (40.7-100%; P=0.006) and CD56, with 61.0% (1.5-99.2%) vs. 98.3% (0.1-100%; P<0.001) expression in malignant PCs.
The study involved 46 patients with MM, and analyzed the prognostic significance of the expression of cluster of differentiation (CD)45, CD56 and mature plasma cell (MPC)-1, and other factors including the International Staging System (ISS) stage, age, gender, the immunoglobulin subtype and the treatment line number prior to bortezomib treatment.
The t(11;14) MM group was associated with a significantly higher positive rate of B-lineage associated antigens CD20 and CD79a as well as the lack of CD56 expression. t(11;14) was less likely to be accompanied by 13q14 deletion than 13q14 deletion frequency in non-t(11;14) population (p=0.026), and fewer patients displaying t(11;14) were identified as belonging to the high-risk cytogenetic group due to the extremely low incidence of t(4;14) and t(14;16).
We analyzed 102 cases of plasma cell neoplasm by flow cytometric immunophenotyping for expression of CD56 and CD117 and correlated the results with immunohistochemical and cytogenetic findings.
Plasma cell myelomas with t(11;14)(q13;q32) were frequently CD20(+) (46.4%) and CD56(-) (53.8%) and had a nonhyperdiploid karyotype (97.6%) with frequent 13q deletion (33.3%).Of 42 cases, 19 (45.2%) expressed CD23.
FOXP2 (>10% nuclear positivity) was detectable in 90.2% of MM (55/61) and 90.9% of MGUS (10/11) patients, showing more frequent expression than CD56 and labelling 75% of CD56-negative MM (9/12).
Our findings propose four potential activators of the CD56 promoter and for CD56 to be involved in proliferation and anti-apoptosis, leading to disease progression in MM.
Our data indicates that p53 nuclear expression but not CD56 expression, along with increased proliferation index is associated with disease progression from intramedullary to extramedullary sites in MM.
In conclusion, CD56 expression carries no distinct adverse prognosis and the lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM.
In summary, our results indicate that lack of CD56 expression on MM cells is not a prognostic marker in patients treated with high-dose chemotherapy, but is associated with t(11;14).
We also report that CD56-negative MM is the unique entity characterized by poor prognosis with high incidence of extramedullary disease, Bence Jones protein, renal insufficiency, thrombocytopenia and plasmablastic morphology.
In B cell lines and flowsorted CD38++/CD19-/CD56++ myeloma plasma cells (N = 14) the c-maf/GAPDH and IL-4/GAPDH ratios were determined simultaneously using real time RT-PCR.
We report on the different expression of CD56 and CD44 in plasma cells (PCs) simultaneously collected from bone marrow, extramedullary locations and peripheral blood in seven patients with multiple myeloma.
Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens.
Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM.