The geographical distribution of clonal hematopoiesis-associated mutations among patients diagnosed with myeloid neoplasms

Abstract Background: The presence of clonal hematopoiesis driver mutations has been associated with an increased risk of developing hematological neoplasms. These mutations are believed to be necessary for stem cells' fitness to sustain the production of progenies. Aging is a well-established biological incubator for clonal hematopoiesis; however, studies from regions where hematological neoplasms are prevalent at a younger age are lacking, which hinders our understanding of how early in life these mutations can be initiated. Additionally, the geographical distribution of affected cases would be relevant in guiding further studies to elaborate on potential non-mutational factors. Method: After obtaining ethical approval, we retrospectively reviewed our electronic medical records from inception to December 2024 and identified 571 patients who underwent next-generation sequencing as part of their evaluation for myeloid neoplasms at our center. Results: Our analysis revealed that the ASXL1 mutation (11%) was the most prevalent among patients aged 20s year, followed by TET2 (8%) and U2AF1 (6%). The prevalence of ASXL1 mutations continued among 30s-year and 40s-year age groups. DNMT3A (6%) had an earlier peak among 30s-year age group before it became prevalent again within older age groups. There was a nadir in the frequency of TET2 mutations among our tested older patients. We did not observe any variances in the prevalence of these mutations according to gender, with the ASXL1 mutation being the most prevalent, followed by TET2 and DNMT3A mutations. The prevalence of ASXL1 mutation was the highest (17%) in patients diagnosed with myeloproliferative neoplasms (193 patients), followed by TP53 (12%) in patients diagnosed with myelodysplastic syndromes/neoplasms (84 patients), and RUNX1 (10%) in patients diagnosed with acute myeloid leukemia. According to patients' geographic location, TET2 mutation was common (14%) among patients living at the Northern Region (63 patients), RUNX1 (11%) among patients living at the Southern Region (91 patients), TP53 (17%) among patients residing at the Eastern Region (29 patients), TET2 (16%) among patients living at the Western Region (153 patients), and ASXL1 (12%) among patients residing at the Central Region (186 patients). Conclusion: Despite the potential limitation of analyzing determinants of clonal hematopoiesis at the time of myeloid disease evolution, our data highlight potential environmental factors that could contribute to the epigenetic process of disease development. Recently, clonal tracking studies have uncovered the role of clonal growth rate in the progression of myeloid neoplasms. Further studies to examine the causal correlations between the occurrence and expansion of these clonal mutations and their environmental determinants will be insightful.