The microenvironment in mature B-cell malignancies: a target for new treatment strategies

• Published in: Blood Vol. 114; no. 16; pp. 3367 - 3375
• Main Authors: Burger, Jan A., Ghia, Paolo, Rosenwald, Andreas, Caligaris-Cappio, Federico
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2009; Americain Society of Hematology; American Society of Hematology
• Series: Review Article
• Subjects: Animals; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; Bone Marrow - metabolism; Bone Marrow - pathology; Cell Communication; Drug Resistance, Neoplasm; Hematologic and hematopoietic diseases; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - pathology; Hematologic Neoplasms - therapy; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoid Tissue - metabolism; Lymphoid Tissue - pathology; Medical sciences; Review; Stromal Cells - metabolism; Stromal Cells - pathology; Antineoplastic agent; Human; Treatment; Hematology; Targeted therapy; Cell microenvironment; Accessory cell; Malignant hemopathy; B-Lymphocyte; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-06-225326

Despite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.