Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies

Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.