Therapeutic molecules targeting the malignant B cell microenvironment of chronic lymphocytic leukemia

  • Georgiana Ene SUUB
  • Ana Maria Vladareanu Hematology Clinic, University Emergency Hospital Bucharest
  • Horia Bumbea Hematology Clinic, University Emergency Hospital Bucharest
Keywords: chronic lymphocytic leukemia, microenvironment, malignant B cell, treatment.

Abstract

Although valuable advances have been made in the hematological field over the past years, most of the B-cell malignancies remain incurable, as malignant B cells retain the ability to respond to a variety of microenvironment signals, providing additional opportunities in the development of therapeutic interactions.
The role that the microenvironment has in the natural history of malignant B cell of chronic lymphocytic leukemia (CLL) appears to favor the development of new treatment modalities aimed at interrupting the interaction between malignant B cells and microenvironment. At this moment, the therapeutic approaches whose target is the CLL microenvironment or the signaling pathways associated with CLL microenvironment are one of the most important therapeutic strategy. Interactions taking place within the tumor microenvironment are targeted by multiple clinical trials, and preliminary results are favorable.
Chronic Lymphocytic Leukemia (CLL) is a size of complexity because leukemic cells are grown and protected by anti-cancer therapies by the components constituting the tumor microenvironment in lymphoid organs (e.g., endothelial cells, dendritic cells (CD), T cells, myeloid-derived suppressor cells (MDSCs), monocyte-derived nurse-like cells (NLC))[1]
Current standard therapy in CLL combines chemotherapy with an anti-CD20 monoclonal antibody. This combination induces substantial toxicity and is not curative, as most patients relapse. Recent advances using kinase inhibitors, such as ibrutinib and idelalisib or BCL2 signaling inhibitors e.g Venetoclax, indicate a major change promising to treat chronic lymphocytic leukemia without chemotherapy. At present, these therapeutic agents do not provide complete responses and should be administered continuously by the patient in order to avoid recurrence/relapse of the disease. Resistance to ibrutinib has already been detected in patients with high genetic risk. [2] This problem requires the identification of therapies that combine agents with distinct mechanisms of action.

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Published
2019-07-05
How to Cite
Ene, G., Vladareanu, A., & Bumbea, H. (2019). Therapeutic molecules targeting the malignant B cell microenvironment of chronic lymphocytic leukemia. Romanian Journal of Clinical Research, 2(1), 17-29. https://doi.org/10.33695/rjcr.v2i1.18
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Articles