• Prabhjot Kaur
Part of the Molecular and Translational Medicine book series (MOLEMED)


Microenvironment is the supporting network that works as a team through cell–cell contacts and active molecular cross talk. These are thought to be critical for homing of cells to distinct microenvironments that provide supportive growth and regulatory factors. The development of normal B cells in the bone marrow from early progenitors and later as mature B cells in the secondary lymphoid organs where they are exposed to antigen within the germinal centers (GCs) requires their interaction with their microenvironment including the stromal cells, T cells, and chemokines along with their unique transcription factors. These signals are required for B-cell survival and select those that will become memory cells; otherwise the B cells undergo programmed cell death. Tumor cells too derive their ability to transit to specific organs by co-opting the same tissue-homing mechanisms used by benign leukocytes. CLL cells, like healthy B cells, become activated upon antigen ligation to the B-cell receptor (BCR), resulting in proliferation and differentiation. This is further enhanced by cytokine stimulation, chemokines, or cell–cell contact. The lymph nodes and bone marrow provide a protective niche for CLL cells, enabling progression of the disease. Proliferation centers in CLL cells are different from the normal lymph node germinal centers. The altered microenvironment that accounts for the difference between the two and makes proliferation centers conducive to disease progression is explained. Current treatment modalities appear to eradicate malignant CLL cells less efficiently in the bone marrow and lymph nodes than in peripheral blood. Patients initially achieve remission only to develop recurrent disease. This indicates a significant role of the tissue microenvironment in supporting CLL cell survival and enabling them to evade the toxic effects of chemotherapy. B-CLL cells undergo spontaneously death in vitro. So where do they get their survival signals from? What are the cytokines, cell–cell interactions, and cell–matrix interactions that promote CLL survival? What is the role of integrins in CLL biology and prognosis? What is the role of CXCR4–CXCL12 axis in CLL therapeutics? All these and more questions are addressed in this chapter.


Microenvironment Cytokines Cell–cell interactions Cell–matrix interactions Integrins CD49d CXCR4–CXCL12 axis “Nurselike” cells (NLCs) 


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Prabhjot Kaur
    • 1
  1. 1.Department of PathologyDartmouth Hitchcock Medical Center and Geisel School of Medicine at Dartmouth 1 Medical Center DriveLebanonUSA

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