The groundbreaking map detailing the significant changes in the blood system throughout a person’s life may influence how acute myeloid leukemia and other blood disorders are treated.
Researchers at the University of California San Diego School of Medicine, along with their colleagues, have created a detailed map illustrating the substantial shifts in the blood system throughout human life.
The research team analyzed the gene expression of over 58,000 unique hematopoietic (blood) stem cells at seven different life stages, ranging from early fetal development to old age. They observed consistent shifts in the types of blood cells produced, tailored to the functional needs corresponding to each stage of life:
- During the early prenatal stage, the production of myeloid cells occurs post-conception. These include tissue-resident macrophages, crucial immune cells that support the initial development of organs, followed by a surge in the second trimester that necessitates the creation of red blood cells to efficiently deliver oxygen to the developing fetus.
- At the time of birth, the focus shifts towards the production of lymphoid cells, which are critical for establishing long-term immunity as newborns encounter the external environment and its various pathogens. Lymphoid cells remain prevalent throughout childhood.
- As individuals transition into adulthood, the generation of lymphoid cells decreases while myeloid cell production gradually increases once more.
The study also revealed that the evolution of blood cell types throughout life can significantly impact the development of blood cancers. The researchers categorized acute myeloid leukemia cells based on their similarity to the gene expression of stem cells at various life stages, discovering that the typical stem cell age most akin to leukemia cells in patients can differ widely, no matter the patient’s actual age.
Interestingly, patients whose leukemia cells exhibited characteristics more akin to younger blood cell production had a significantly poorer prognosis compared to those whose leukemia cells resembled older blood cell characteristics. The research team suspects that these cancer cells might reconfigure themselves to exhibit fetal-like traits, contributing to their more aggressive nature. Further analysis pinpointed seven transcription factor genes that play a crucial role in determining whether leukemia cells appear more youthful or aged.
Future research aims to determine if the disease exploits the rapid growth potential of young blood cells, making leukemia more deadly in patients than it would be with older, less active blood cells. They are also optimistic about the possibility of reprogramming leukemia cells in the future.
“If we can create medications that target the key elements driving the production of young blood cells, it might allow the leukemia to resemble older blood cells, potentially making it simpler to treat,” stated Hojun Li, M.D., Ph.D., an assistant professor of pediatrics at UC San Diego School of Medicine, a member of UC San Diego Moores Cancer Center, and an attending physician at Rady Children’s Hospital-San Diego. He co-led the study with R. Grant Rowe, M.D., Ph.D., an assistant professor of pediatrics at Boston Children’s Hospital, Harvard Medical School.
