When are idiopathic and clonal cytopenias of unknown significance (ICUS or CCUS)?
- PMID: 34889436
- PMCID: PMC8791167
- DOI: 10.1182/hematology.2021000272
When are idiopathic and clonal cytopenias of unknown significance (ICUS or CCUS)?
Abstract
Rapid advances in sequencing technology have led to the identification of somatic mutations that predispose a significant subset of the aging population to myeloid malignancies. Recently recognized myeloid precursor conditions include clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS). These conditions can present diagnostic challenges and produce unwarranted anxiety in some instances. While the risk of progression to myeloid malignancies is very low in CHIP, true CCUS confers an exponential increase in risk. Idiopathic cytopenia of unknown significance (IDUS) lacks the predisposing genetic mutations and has a variable course. In this review we define the early myeloid precursor conditions and their risk of progression. We present our diagnostic approach to patients with unexplained cytopenias and discuss the clinical consequences of CHIP and CCUS.
Copyright © 2021 by The American Society of Hematology.
Conflict of interest statement
Afaf E. W. G. Osman: no competing financial interests to declare.
Figures


Similar articles
-
The Clinical Challenge of Idiopathic Cytopenias of Undetermined Significance (ICUS) and Clonal Cytopenias of Undetermined Significance (CCUS).Curr Hematol Malig Rep. 2019 Dec;14(6):536-542. doi: 10.1007/s11899-019-00547-3. Curr Hematol Malig Rep. 2019. PMID: 31696381 Review.
-
CHIP, CCUS, and Other Acronyms: Definition, Implications, and Impact on Practice.Am Soc Clin Oncol Educ Book. 2019 Jan;39:400-410. doi: 10.1200/EDBK_239083. Epub 2019 May 17. Am Soc Clin Oncol Educ Book. 2019. PMID: 31099654 Review.
-
Clonal cytopenia of undetermined significance (CCUS) with dysplasia is enriched for MDS-type molecular findings compared to CCUS without dysplasia.Eur J Haematol. 2021 Apr;106(4):500-507. doi: 10.1111/ejh.13574. Epub 2021 Jan 15. Eur J Haematol. 2021. PMID: 33386622
-
[The state of the art: diagnosis and therapeutic interventions of clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance].Zhonghua Xue Ye Xue Za Zhi. 2025 Jan 14;46(1):5-8. doi: 10.3760/cma.j.cn121090-20241228-00600. Zhonghua Xue Ye Xue Za Zhi. 2025. PMID: 40059676 Free PMC article. Chinese.
-
Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis.Ann Lab Med. 2019 Nov;39(6):509-514. doi: 10.3343/alm.2019.39.6.509. Ann Lab Med. 2019. PMID: 31240877 Free PMC article. Review.
Cited by
-
Natural killer cells' functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes.Nat Commun. 2025 Apr 11;16(1):3450. doi: 10.1038/s41467-025-58662-0. Nat Commun. 2025. PMID: 40216768 Free PMC article.
-
Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease.Diagnostics (Basel). 2022 Jul 2;12(7):1613. doi: 10.3390/diagnostics12071613. Diagnostics (Basel). 2022. PMID: 35885518 Free PMC article. Review.
-
Molecular Studies for the Early Detection of Philadelphia-Negative Myeloproliferative Neoplasms.Int J Mol Sci. 2023 Aug 11;24(16):12700. doi: 10.3390/ijms241612700. Int J Mol Sci. 2023. PMID: 37628880 Free PMC article. Review.
-
How I treat anemia in older adults.Blood. 2024 Jan 18;143(3):205-213. doi: 10.1182/blood.2022017626. Blood. 2024. PMID: 36827619 Free PMC article.
-
Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.Cancer Cell Int. 2025 May 10;25(1):175. doi: 10.1186/s12935-025-03793-z. Cancer Cell Int. 2025. PMID: 40349084 Free PMC article. Review.
References
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources