Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
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The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.
Abstract
The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.
참고문헌 (36)
- Valent P, "Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference", Leuk Res, 31, pp.727~736 (2007)
- Valent P, "Proposed minimal diagnostic criteria for myelodysplastic syndromes(MDS)and potential pre-MDS conditions", Oncotarget, 8, pp.73483~73500 (2017)
- Laurie CC, "Detectable clonal mosaicism from birth to old age and its relationship to cancer", Nat Genet, 44, pp.642~650 (2012)
- Jacobs KB, "Detectable clonal mosaicism and its relationship to aging and cancer", Nat Genet, 44, pp.651~658 (2012)
- Forsberg LA, "Non-heritable genetics of human disease : spotlight on post-zygotic genetic variation acquired during lifetime", J Med Genet, 50, pp.1~10 (2013)
- Jaiswal S, "Age-related clonal hematopoiesis associated with adverse outcomes", N Engl J Med, 371, pp.2488~2498 (2014)
- Genovese G, "Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence", N Engl J Med, 371, pp.2477~2487 (2014)
- Zink F, "Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly", Blood, 130, pp.742~752 (2017)
- Steensma DP, "Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes", Blood, 126, pp.9~16 (2015)
- Welch JS, "The origin and evolution of mutations in acute myeloid leukemia", Cell, 150, pp.264~278 (2012)
- Haferlach T, "Landscape of genetic lesions in 944 patients with myelodysplastic syndromes", Leukemia, 28, pp.241~247 (2014)
- Papaemmanuil E, "Clinical and biological implications of driver mutations in myelodysplastic syndromes", Blood, 122, pp.3616~3627 (2013)
- Rollison DE, "Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs", Blood, 112, pp.45~52 (2008)
- Jaiswal S, "Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease", N Engl J Med, 377, pp.111~121 (2017)
- Gibson CJ, "Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma", J Clin Oncol, 35, pp.1598~1605 (2017)
- Kwok B, "MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance", Blood, 126, pp.2355~2361 (2015)
- Cargo CA, "Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression", Blood, 126, pp.2362~2365 (2015)
- Malcovati L, "The shadowlands of MDS : idiopathic cytopenias of undetermined significance(ICUS)and clonal hematopoiesis of indeterminate potential(CHIP)", Hematology Am Soc Hematol Educ Program, 2015, pp.299~307 (2015)
- Malcovati L, "Clinical significance of somatic mutation in unexplained blood cytopenia", Blood, 129, pp.3371~3378 (2017)
- Malcovati L, "SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts", Blood, 126, pp.233~241 (2015)
- Thol F, "Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis", Leukemia, 31, pp.1286~1295 (2017)
- Buscarlet M, "DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions", Blood, 130, pp.753~762 (2017)
- Perdigones N, "Clonal hematopoiesis in patients with dyskeratosis congenita", Am J Hematol, 91, pp.1227~1233 (2016)
- Yoshizato T, "Somatic mutations and clonal hematopoiesis in aplastic anemia", N Engl J Med, 373, pp.35~47 (2015)
- Ogawa S, "Clonal hematopoiesis in acquired aplastic anemia", Blood, 128, pp.337~347 (2016)
- Papaemmanuil E, "Genomic classification and prognosis in acute myeloid leukemia", N Engl J Med, 374, pp.2209~2221 (2016)
- Gelsi-Boyer V, "Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases", J Hematol Oncol, 5, pp.12~ (2012)
- Smith ZD, "DNA methylation : roles in mammalian development", Nat Rev Genet, 14, pp.204~220 (2013)
- Steensma DP, "Clinical implications of clonal hematopoiesis", Mayo Clin Proc, 93, pp.1122~1130 (2018)
- Steensma DP, "Clinical consequences of clonal hematopoiesis of indeterminate potential", Blood Adv, 2, pp.3404~3410 (2018)
- Bejar R, "Clinical effect of point mutations in myelodysplastic syndromes", N Engl J Med, 364, pp.2496~2506 (2011)
- Bejar R, "Clinical and genetic predictors of prognosis in myelodysplastic syndromes", Haematologica, 99, pp.956~964 (2014)
- Arber DA, "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia", Blood, 127, pp.2391~2405 (2016)
- Greenberg PL, "Revised international prognostic scoring system for myelodysplastic syndromes", Blood, 120, pp.2454~2465 (2012)
- Schanz J, "New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes(MDS)and oligoblastic acute myeloid leukemia after MDS derived from an international database merge", J Clin Oncol, 30, pp.820~829 (2012)
- Patel JL, "The clinical and laboratory features of clonal hematopoiesis of indeterminate potential", Adv Mol Pathol, 1, pp.37~42 (2018)