Clonal hematopoiesis may precede the diagnosis of aplastic anemia by several years

Aplastic anemia Aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (AA) is a bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndrome resulting from the immune destruction of hematopoietic stem cells stem cells: Cells in the body that develop into other cells. There are two main sources of stem cells. Embryonic stem cells come from human embryos and are used in medical research. Adult stem cells in the body repair and maintain the organ or tissue in which they are found. Blood-forming (hemapoietic) stem… . Clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. (CH) is characterized by expansion of progenitor hematopoietic stem cells that harbor leukemogenic driver mutations. It has previously been shown that individuals with AA have a high prevalence of CH. However, the association between CH and AA remains unknown. We conducted a prospective, matched cohort study within the UK Biobank from 2006 to 2022. Individuals with CH were ascertained based on whole-exome sequencing data. For each individual with CH, we randomly selected 10 individuals without CH matched by sex, birth year, and ethnicity from the study population. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of AA associated with CH using a Cox regression model. We also studied the association by different mutations of CH. We identified 14 471 individuals with CH, and 144 323 matched individuals free of CH. Individuals with CH had a higher risk of AA (HR, 2.72; 95% CI, 2.16-3.43) than the reference group. The increase was greater for individuals with CH mutations in SRSF2 (HR, 19.35; 95% CI, 11.07-33.80), TET2 (HR, 4.45; 95% CI, 3.14-6.29), ASXL1 (HR, 2.06; 95% CI, 1.06-4.00), or DNMT3A (HR, 1.88; 95% CI, 1.31-2.70). In conclusion, CH may precede the diagnosis of AA, particularly in those with SRSF2, TET2, ASXL1, and DNMT3A mutations. Further studies are needed to understand the nature of this association and potential shared pathogenic mechanisms between CH and AA.