淋巴细胞损伤的三个潜在来源与淋巴性白血病和淋巴瘤的发生发展
Three potential sources of cell injuries of lymphoid cells associated with developments of lymphoid leukemia and lymphoma
摘要：
类淋巴细胞白血病（LL）和淋巴瘤是从淋巴样细胞（LC）发展而来的血液癌症。为了了解LC细胞转化的原因和机制，我们研究了LC细胞损伤的潜在来源，并分析了DNA变化如何在LC中产生和积累。I.有助于LC细胞转化的DNA变化可在骨髓、胸腺、淋巴结（LN）和/或淋巴组织（LT）中的LC中产生。在LN/LT中，病原体感染可能是LC细胞损伤的主要原因。在骨髓腔中，骨生长和修复过程中反复的骨重建，通过产生有毒物质，可能是造血细胞（包括造血干细胞（hematopoietic stem cells，HSCs）和发育中的LCs）受损的原因之一。在胸腺中，胸腺退化和基质细胞的死亡可能是发育中的T细胞的损伤因素。二. DNA点突变（PDM）和染色体改变（CC）是DNA改变的两种主要类型。CC包括数字CC（NCC）和结构CC（SCC）。PDM/SCC的产生可能是DNA断裂时DNA错误修复的结果。NCC的产生是细胞分裂功能障碍的结果。三.重复的细胞损伤和细胞增殖驱动LC和HSC中DNA变化的积累。然而，DNA变化的长期积累主要发生在包括HSC和记忆细胞在内的长寿命干细胞中。总之，LC中的DNA变化是由于重复的细胞损伤和重复的细胞增殖而产生和积累的; LC的细胞损伤的三个潜在来源可能是：重复的骨重塑、长期的胸腺退化和重复的病原体感染。
英文摘要：
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.
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