Three potential sources of cell injuries of lymphoid cells associated with developments of lymphoid leukemia and lymphoma

TL;DR

This paper investigates three main sources of cell injuries in lymphoid cells—bone remodeling, thymic involution, and infections—that contribute to DNA damage and the development of lymphoid leukemia and lymphoma.

Contribution

It identifies specific biological processes causing DNA damage in lymphoid cells and explains how these injuries lead to leukemia and lymphoma development.

Findings

DNA changes originate in marrow, thymus, lymph nodes, and lymphoid tissues.

Repeated injuries and proliferation lead to DNA damage accumulation.

Long-lived stem cells mainly accumulate DNA changes over time.

Abstract

Lymphoid leukemia (LL) and lymphoma are blood cancers developed from lymphoid cells (LCs). To understand the cause and the mechanism of cell transformation of a LC, we studied the potential sources of cell injuries of LCs and analyzed how DNA changes are generated and accumulate in LCs. I. The DNA changes that contribute to cell transformation of a LC can be generated in the LCs in marrow, thymus, lymph nodes (LNs), and/or lymphoid tissues (LTs). In LNs/LTs, pathogen-infections may be the main cause for cell injuries of LCs. In marrow cavity, repeated bone-remodeling during bone-growth and bone-repair, by producing toxic substances, may be a source of damage to hematopoietic cells, including hematopoietic stem cells (HSCs) and developing LCs. In thymus, thymic involution and death of stromal cells may be a damaging factor for the developing T-cells. II. Point DNA mutation (PDM) and chromosome change (CC) are the two major types of DNA changes. CCs include numerical CCs (NCCs) and structural CCs (SCCs). Generation of a PDM/SCC may be a result of Misrepair of DNA on DNA breaks. Generation of NCC is rather a consequence of dysfunction of cell division. III. Repeated cell injuries and cell proliferation drive the accumulation of DNA changes in LCs and HSCs. However, long-term accumulation of DNA changes occurs mainly in long-living stem cells including HSCs and memory cells. In conclusion, the DNA changes in LCs are generated and accumulate as a consequence of repeated cell injuries and repeated cell proliferation; and three potential sources of cell injuries of LCs may be: repeated bone-remodeling, long-term thymic involution, and repeated pathogen-infections.