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Lymphoid leukemia (LL) and lymphoma are blood cancers developed from lymphoidcells (LCs). To understand the cause and the mechanism of cell transformationof a LC, we studied the potential sources of cell injuries of LCs and analyzedhow DNA changes are generated and accumulate in LCs. I. The DNA changes thatcontribute to cell transformation of a LC can be generated in the LCs inmarrow, 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 marrowcavity, repeated bone-remodeling during bone-growth and bone-repair, byproducing toxic substances, may be a source of damage to hematopoietic cells,including hematopoietic stem cells (HSCs) and developing LCs. In thymus, thymicinvolution and death of stromal cells may be a damaging factor for thedeveloping T-cells. II. Point DNA mutation (PDM) and chromosome change (CC) arethe two major types of DNA changes. CCs include numerical CCs (NCCs) andstructural CCs (SCCs). Generation of a PDM/SCC may be a result of Misrepair ofDNA on DNA breaks. Generation of NCC is rather a consequence of dysfunction ofcell division. III. Repeated cell injuries and cell proliferation drive theaccumulation of DNA changes in LCs and HSCs. However, long-term accumulation ofDNA changes occurs mainly in long-living stem cells including HSCs and memorycells. In conclusion, the DNA changes in LCs are generated and accumulate as aconsequence of repeated cell injuries and repeated cell proliferation; andthree potential sources of cell injuries of LCs may be: repeatedbone-remodeling, long-term thymic involution, and repeated pathogen-infections.

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