Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Concise Review
  • Published:

CHIP, ICUS, CCUS and other four-letter words

Abstract

Clonal hematopoiesis can be identified by the presence of somatic mutations in blood or bone marrow even in individuals without a myeloid malignancy. Advances in DNA sequencing have led to the discovery that clonal hematopoiesis is remarkably common and occurs in a wide variety of settings, each often described by unique acronym. These distinctions can be useful as the implications of clonal hematopoiesis depend almost entirely on the clinical context in which it is identified. However, some generalizations can be made. The prevalence of clonal hematopoiesis increases with age, particularly after the fifth decade of life. Clonal hematopoiesis in normal individuals with very small clones is typically benign, while patients with clinically abnormal hematopoiesis, larger clones and more driver gene mutations appear to be at much greater risk. Understanding the significance of clonal hematopoiesis in the various contexts in which it occurs can influence how physicians assess risk, select therapies and counsel their patients. This concise review examines the implications of clonal hematopoiesis in several settings, including normal aging, aplastic anemia, unexplained cytopenias and patients receiving cytotoxic chemotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Link DC, Walter MJ . 'CHIP'ping away at clonal hematopoiesis. Leukemia 2016; 30: 1633–1635.

    Article  CAS  Google Scholar 

  2. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014; 371: 2488–2498.

    Article  Google Scholar 

  3. Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014; 371: 2477–2487.

    Article  Google Scholar 

  4. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014; 20: 1472–1478.

    Article  CAS  Google Scholar 

  5. Busque L, Patel JP, Figueroa ME, Vasanthakumar A, Provost S, Hamilou Z et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet 2012; 44: 1179–1181.

    Article  CAS  Google Scholar 

  6. Zink F, Stacey SN, Norddahl GL, Frigge ML, Magnusson OT, Jonsdottir I et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 2017; e-pub ahead of print 8 may 2017 doi:10.1182/blood-2017-02-769869.

  7. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 2015 Jul 02; 126: 9–16.

    Article  CAS  Google Scholar 

  8. Takahashi K, Wang F, Kantarjian H, Doss D, Khanna K, Thompson E et al. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. Lancet Oncol 2016; 18: 100–111.

    Article  Google Scholar 

  9. Gillis NK, Ball M, Zhang Q, Ma Z, Zhao Y, Yoder SJ et al. Clonal haemopoiesis and therapy-related myeloid malignancies in elderly patients: a proof-of-concept, case-control study. Lancet Oncol 2017; 18: 112–121.

    Article  Google Scholar 

  10. Gibson CJ, Lindsley RC, Tchekmedyian V, Shi J, Mar BG, Jaiswal S et al. Clonal hematopoiesis associated with adverse outcomes following autologous stem cell transplantation for non-hodgkin lymphoma. Blood 2016; 128: 986–986.

    Article  Google Scholar 

  11. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 2015; 518: 552–555.

    Article  CAS  Google Scholar 

  12. McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J et al. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep 2015; 10: 1239–1245.

    Article  CAS  Google Scholar 

  13. Young AL, Challen GA, Birmann BM, Druley TE . Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nature Commun 2016; 7: 12484.

    Article  CAS  Google Scholar 

  14. Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K, Townsley D et al. Somatic mutations and clonal hematopoiesis in aplastic anemia. N Engl J Med 2015; 373: 35–47.

    Article  CAS  Google Scholar 

  15. Stanley N, Olson TS, Babushok DV . Recent advances in understanding clonal haematopoiesis in aplastic anaemia. Br J Haematol 2017; 177: 509–525.

    Article  CAS  Google Scholar 

  16. Kulasekararaj AG, Jiang J, Smith AE, Mohamedali AM, Mian S, Gandhi S et al. Somatic mutations identify a sub-group of aplastic anemia patients that progress to myelodysplastic syndrome. Blood 2014; 18: 2014–2005.

    Google Scholar 

  17. Ogawa S . Clonal hematopoiesis in acquired aplastic anemia. Blood 2016; 128: 337–347.

    Article  CAS  Google Scholar 

  18. Valent P, Bain BJ, Bennett JM, Wimazal F, Sperr WR, Mufti G et al. Idiopathic cytopenia of undetermined significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), and their distinction from low risk MDS. Leuk Res 2012; 36: 1–5.

    PubMed  Google Scholar 

  19. Kwok B, Hall JM, Witte JS, Xu Y, Reddy P, Lin K et al. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood 2015; 126: 2355–2361.

    Article  CAS  Google Scholar 

  20. Cargo CA, Rowbotham N, Evans PA, Barrans SL, Bowen DT, Crouch S et al. Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. Blood 2015; 126: 2362–2365.

    Article  CAS  Google Scholar 

  21. Kern W, Meggendorfer M, Haferlach C, Haferlach T . Integrated diagnostic approach for suspected myelodysplastic syndrome as a basis for advancement of diagnostic criteria. Blood 2016; 128: 299–299.

    Google Scholar 

  22. Malcovati L, Gallì A, Travaglino E, Ambaglio I, Rizzo E, Molteni E et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 2017; e-pub ahead of print 19 April 2017 doi:10.1182/blood-2017-01-763425.

  23. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014; 506: 328–333.

    Article  CAS  Google Scholar 

  24. Wong TN, Miller CA, Klco JM, Petti A, Demeter R, Helton NM et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016; 127: 893–897.

    Article  CAS  Google Scholar 

  25. Thol F, Klesse S, Kohler L, Gabdoulline R, Kloos A, Liebich A et al. Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis. Leukemia 2017; 31: 1286–1295.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Bejar.

Ethics declarations

Competing interests

Dr. Bejar has received honoraria as a consultant and advisory member to Genoptix and Foundation Medicine. He has received royalties for IP licensed to Genoptix and has received research funding from Celgene.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bejar, R. CHIP, ICUS, CCUS and other four-letter words. Leukemia 31, 1869–1871 (2017). https://doi.org/10.1038/leu.2017.181

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2017.181

This article is cited by

Search

Quick links