Francesco Gervasi | Search PubMed

PubMed2004

Targeting multiple myeloma cells and their bone marrow microenvironment.

Although multiple myeloma (MM) is sensitive to chemotherapy and radiation therapy, long-term disease-free survival is rare, and MM remains incurable despite conventional and high-dose therapies. Direct (cell-cell contact) and soluble (via cytokines) forms of interactions between MM cells and bone marrow stroma regulate growth, survival, and homing of MM cells. These interactions also play a critical role in angiogenesis and in myeloma bone disease. In recent years, several studies have established the biologic significance of cytokines in MM pathogenesis and delineated signaling cascades mediating their effects, providing the framework for related novel therapies targeting not only the MM cell, but also the bone marrow microenvironment.

Antineoplastic Agents↗

PubMed2004

Flow cytometric immunophenotyping analysis of patterns of antigen expression in non-Hodgkin's B cell lymphoma in samples obtained from different anatomic sites.

Multiparametric clinical flow cytometry has evolved from two-parameter quantitative assessment of lymphocytes to assessment of many qualitative parameters of suspensions obtained from bone marrow, peripheral blood, and lymph nodes for hematopathology. Nowadays, lymphoma immunophenotyping is a necessary complement to morphology and molecular parameters in the diagnosis and monitoring of human hematopoietic malignancies. The aim of the present study was to determine whether immunophenotypic differences could be used to distinguish between non-Hodgkin's B cell lymphoma (NHL-B) and the normal B cell subpopulation by assessing the variability in the patterns of expression of some lymphoid antigens (CD5, CD19, FMC7, CD23, CD20, CD79b, CD38, CD22, CD10, sIgkappa, sIglambda, mIgA, mIgG, mIgM, and mIgD) in specimens obtained from patients with NHL-B. We have studied peripheral blood samples, lymph node suspensions, and bone marrow specimens from 20 patients with malignant lymphoma and from controls without oncohematologic disease. Some patients showed stable patterns of antigen expression that remained unchanged over time and were consistent from one specimen to another. Other patients showed more variability in the pattern of antigen expression from different specimens. The two-way cluster analysis of antigens revealed three patterns of expression: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD45); (2) most cells in most cases negative (CD10, mIgG, CD22, CD23,CD38); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD22, CD38, CD79b, FMC7, mIgD, mIgM, mIgA, mIgG, sIgkappa, sIglambda). The expression of several antigens was strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were CD19/CD45; CD19/CD79b; CD23/Igkappa; and CD45/CD79b. Our results suggest that different factors may determine the stability or the variability of such multiantigen expression, particularly the biology and function of the different antigens and the mechanisms of disease dissemination and progression.

Aged↗

PubMed2002

Multidimensional flow cytometry immunophenotyping of hematologic malignancy.

Immunophenotyping of hematologic malignancies represents one of the most relevant clinical applications of flow cytometry. Classically, leukemic/lymphomatous cells have been considered to reflect the immunophenotypic characteristics of different precursors and mature healthy cells blocked at certain differentiation stages. Recently, accumulating evidence has shown that neoplastic cells display several aberrant phenotypic patterns. These aberrant phenotypes are believed to reflect genetic abnormalities present in pathologic cells, and recent data have shown that at least in acute leukemias, myelodysplastic syndromes, chronic lymphoproliferative disorders, and plasma cell dyscrasias, they may be present in almost all patients. The aim of this work is to review recent advances in flow cytometry and the role of gating strategies more useful in the identification and characterization of neoplastic cells of different hematologic malignancies.

ADP-ribosyl Cyclase↗