The effect of microenvironmental factors on the development of myeloma cells

Abstract

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells (PCs) in the bone marrow and other tissues. Although there are several new therapies, MM remains fatal. The interaction between MM cells and the bone marrow microenvironment promotes drug resistance and cancer cells survival. In our present work, we compared the antigen expression pattern of normal and pathological PCs and investigated the possible connections between various surface receptors, adhesion molecules, and recurrent genetic aberrations. We showed that the expression of CD29, CD27, and CD81 is lower in MM cells than in normal PCs. We found correlation of chromosome 11 hyperdiploidity and the decrease of CD27 expression. We demonstrated that MM cells with CD20 positivity also have CD28 expression. Multiple myeloma patients with active CD29 showed better response to treatment. Our results suggest that these changes may result in an alteration of the interaction between stromal cell and MM cell facilitating cell survival and the development of a more aggressive and resistant phenotype.

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)

“…Here, we confirm that PB CTPC from MM and MGUS patients are immunophenotypically more immature than their BM counterpart, as reflected by the expression of significantly lower levels of (i) markers that are typically acquired by PC during migration from secondary lymphoid tissues to the BM, such as CD38 and CD138 60 – 64 , and (ii) adhesion molecules that anchor PC to stromal structures such as CD56, CD81, and CD117 60 , 65 – 67 . Of note, here we also show that PB CTPC display lower expression levels of activation/differentiation-associated antigens such as CD27 67 and Vs38c, a rough endoplasmic reticulum protein directly linked to a high rate of protein (i.e., Ig) synthesis and secretion 64 , 68 , 69 . In line with previous observations, PB CTPC detected in this large series of patients also tended to show lower levels of expression (vs. BMPC) of the Ki67-proliferation associated marker 9 , 25 , 55 , 56 .…”

Immune profiles in Bone marrow to predict induce therapy response for multiple myeloma patients

“…It was also well known that immune system cells, and especially B cells, can vary their phenotype under the in uence of MM microenvironment. [31] Long-term, large sample, and prospective studies were needed to con rm whether the immune cell subsets analyzed, based on the ow cytometry methods proposed in this paper, have a predictive value for the prognosis of MM patients.…”

Protein-Functionalized Microgel for Multiple Myeloma Cells’ 3D Culture

“…(In this work, we explored nPC adhesion to FN, but this can be easily extrapolated to interactions with other extracellular matrix components.) The environment in which the disease develops is highly complex, with several differentiated microenvironments and multiple cell–cell and cell–ECM component interactions with soluble factors [ 3 , 4 ]. When establishing a model aiming to isolate one of the factors that contributes to the development of the pathology, there is a risk of reaching erroneous conclusions due to the lack of other elements that affect the equation, in particular, the 3D configuration and cell mobility [ 38 , 40 ].…”

“…It is characterized by the proliferation of neoplastic plasma cells (nPCs) in the bone marrow [ 2 ]. The development of a realistic 3D culture system is growing in relevance due to the important role played by the extracellular matrix (ECM) components and the stromal cells in their interactions with nPCs, promoting their survival and generating drug resistance [ 3 , 4 , 5 , 6 ]. Although new therapies have been developed, MM still remains an incurable disease due to the nPCs’ protection against chemotherapy or receptor-targeting drugs [ 7 , 8 , 9 ].…”