在癌症化疗后,造血干细胞的克隆进化
bioRxiv : the preprint server for biology
|June 3, 2024
概括
癌症化疗,特别是梅尔法兰,通过增加突变和促进克隆进化,加速造血干细胞衰老. 这种化疗诱导的基因组不稳定性可能导致与治疗相关的髓状瘤.
科学领域:
- 血液学 血液学 血液学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 正常的造血干细胞和原生细胞 (HSPCs) 累积突变,随着年龄的增长而丧失多样性,易患髓状恶性瘤.
- 癌症化疗对正常HSPCs的基因组完整性和克隆动态的影响尚不清楚.
研究的目的:
- 调查化疗方案对正常HSPCs基因组景观的影响.
- 了解化疗后HSPCs的克隆演变及其与治疗相关的髓状瘤 (t-MNs) 的潜在联系.
主要方法:
- 来自10名多发性髓瘤患者的1,032个单细胞衍生HSPC殖民地的全基因组测序.
- 遗传学分析以重建克隆架构和进化轨迹.
- 对匹配的t-MN样本进行分析,以追踪克隆起源.
主要成果:
- 梅尔法兰治疗显著增加了HSPCs的突变负担,表现出独特的突变特征.
- 化疗诱导了瘤驱动基因 (例如,TET2,PPM1D) 的突变,并促进了融合进化.
- 在治疗后,HSPC的克隆架构模仿了加速的克隆衰老,多个克隆具有恶性潜力.
结论:
- 化疗,特别是梅尔法兰,可以诱导基因组不稳定性,并加速HSPCs的克隆老化.
- 化疗诱导的HSPC变化产生了具有竞争性白血病潜力的基基结构.
- 二次突变对克隆主导和导致t-MNs的恶性转变至关重要.
相关概念视频
Cancer Stem Cells and Tumor Maintenance
4.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.9K
Stem Cell Therapy for Tissue Regeneration
4.0K
Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
4.0K
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
Multipotency of Hematopoietic Stem Cells
3.1K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K
Bone Marrow Sampling and Transplants
324
Bone marrow transplant is a potential cure for several diseases, including cancer and specific genetic disorders. Notably, this procedure is applicable for patients suffering from aplastic anemia, certain types of leukemia, severe combined immunodeficiency disease (SCID), Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, thalassemia, sickle-cell disease, and certain cancers.
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy...
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy...
324
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K


