Clonal hematopoiesis

Clonal hematopoiesis of indeterminate potential, or CHIP, is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells.[1][2][3] As the name suggests, this subpopulation in the blood is characterized by a shared unique mutation in the cells' DNA; it is thought that this subpopulation is "clonally" derived from a single founding cell and is therefore made of genetic "clones" of the founder.[4][5][6][7] The establishment of a clonal population may occur when a stem or progenitor cell acquires one or more somatic mutations that give it a competitive advantage in hematopoiesis over the stem/progenitor cells without these mutations.[1][3] Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as neutral drift in the stem cell population.[8] Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases.[1][9][10] The clonal population may vary in size depending on the person, where it can be less than 2% of the blood or, at the other end, can sometimes grow close to 100%.[4][9] The incidence of clonal hematopoiesis has been found to rise dramatically with age. Recent studies have demonstrated that less than 1% of the population under age 40 but approximately 10-20% of the population over age 70 has observable clonal hematopoiesis.[4][5][6] Having clonal hematopoiesis has been linked to a more than 10-fold increased risk of developing a blood cancer, though the overall likelihood is still low.[4][5] Clonal hematopoiesis does not typically give rise to noticeable symptoms, but does lead to increased risk of cardiovascular disease.[1][5][11] Patients with solid tumors or lymphoma and clonal hematopoiesis have been shown to have an inferior outcome.[12]

  1. ^ a b c d Jan, Max; Ebert, Benjamin L.; Jaiswal, Siddhartha (1 January 2017). "Clonal hematopoiesis". Seminars in Hematology. 54 (1): 43–50. doi:10.1053/j.seminhematol.2016.10.002. PMC 8045769. PMID 28088988.
  2. ^ Sperling, Adam S.; Gibson, Christopher J.; Ebert, Benjamin L. (2017). "The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia". Nature Reviews Cancer. 17 (1): 5–19. doi:10.1038/nrc.2016.112. PMC 5470392. PMID 27834397.
  3. ^ a b Steensma, David P.; Bejar, Rafael; Jaiswal, Siddhartha; Lindsley, R. Coleman; Sekeres, Mikkael A.; Hasserjian, Robert P.; Ebert, Benjamin L. (2 July 2015). "Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes". Blood. 126 (1): 9–16. doi:10.1182/blood-2015-03-631747. PMC 4624443. PMID 25931582.
  4. ^ a b c d Genovese, Giulio; Kähler, Anna K.; Handsaker, Robert E.; Lindberg, Johan; Rose, Samuel A.; Bakhoum, Samuel F.; Chambert, Kimberly; Mick, Eran; Neale, Benjamin M.; Fromer, Menachem; Purcell, Shaun M.; Svantesson, Oscar; Landén, Mikael; Höglund, Martin; Lehmann, Sören; Gabriel, Stacey B.; Moran, Jennifer L.; Lander, Eric S.; Sullivan, Patrick F.; Sklar, Pamela; Grönberg, Henrik; Hultman, Christina M.; McCarroll, Steven A. (25 December 2014). "Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence". The New England Journal of Medicine. 371 (26): 2477–87. doi:10.1056/NEJMoa1409405. PMC 4290021. PMID 25426838.
  5. ^ a b c d Jaiswal, Siddhartha; Fontanillas, Pierre; Flannick, Jason; Manning, Alisa; Grauman, Peter V.; Mar, Brenton G.; Lindsley, R. Coleman; Mermel, Craig H.; Burtt, Noel; Chavez, Alejandro; Higgins, John M.; Moltchanov, Vladislav; Kuo, Frank C.; Kluk, Michael J.; Henderson, Brian; Kinnunen, Leena; Koistinen, Heikki A.; Ladenvall, Claes; Getz, Gad; Correa, Adolfo; Banahan, Benjamin F.; Gabriel, Stacey; Kathiresan, Sekar; Stringham, Heather M.; McCarthy, Mark I.; Boehnke, Michael; Tuomilehto, Jaakko; Haiman, Christopher; Groop, Leif; Atzmon, Gil; Wilson, James G.; Neuberg, Donna; Altshuler, David; Ebert, Benjamin L. (25 December 2014). "Age-related clonal hematopoiesis associated with adverse outcomes". The New England Journal of Medicine. 371 (26): 2488–98. doi:10.1056/NEJMoa1408617. PMC 4306669. PMID 25426837.
  6. ^ a b Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li (1 December 2014). "Age-related mutations associated with clonal hematopoietic expansion and malignancies". Nature Medicine. 20 (12): 1472–78. doi:10.1038/nm.3733. PMC 4313872. PMID 25326804.
  7. ^ McKerrell, T; Park, N; Moreno, T; Grove, CS; Ponstingl, H; Stephens, J; Understanding Society Scientific, Group.; Crawley, C; Craig, J; Scott, MA; Hodkinson, C; Baxter, J; Rad, R; Forsyth, DR; Quail, MA; Zeggini, E; Ouwehand, W; Varela, I; Vassiliou, GS (3 March 2015). "Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis". Cell Reports. 10 (8): 1239–45. doi:10.1016/j.celrep.2015.02.005. PMC 4542313. PMID 25732814.
  8. ^ Zink, Florian; Stacey, Simon N.; Norddahl, Gudmundur L.; Frigge, Michael L.; Magnusson, Olafur T.; Jonsdottir, Ingileif; Thorgeirsson, Thorgeir E.; Sigurdsson, Asgeir; Gudjonsson, Sigurjon A. (2017-01-01). "Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly". Blood. 130 (6): blood–2017–02–769869. doi:10.1182/blood-2017-02-769869. PMC 5553576. PMID 28483762.
  9. ^ a b da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H. (21 April 2017). "Clonal evolution in myelodysplastic syndromes". Nature Communications. 8: 15099. Bibcode:2017NatCo...815099D. doi:10.1038/ncomms15099. PMC 5530598. PMID 28429724.
  10. ^ Gibson, Christopher J.; Lindsley, R. Coleman; Tchekmedyian, Vatche; Mar, Brenton G.; Shi, Jiantao; Jaiswal, Siddhartha; Bosworth, Alysia; Francisco, Liton; He, Jianbo; Bansal, Anita; Morgan, Elizabeth A.; Lacasce, Ann S.; Freedman, Arnold S.; Fisher, David C.; Jacobsen, Eric; Armand, Philippe; Alyea, Edwin P.; Koreth, John; Ho, Vincent; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Nikiforow, Sarah; Forman, Stephen J.; Michor, Franziska; Neuberg, Donna; Bhatia, Ravi; Bhatia, Smita; Ebert, Benjamin L. (9 January 2017). "Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma". Journal of Clinical Oncology. 35 (14): 1598–1605. doi:10.1200/JCO.2016.71.6712. PMC 5455707. PMID 28068180.
  11. ^ Jaiswal, Siddhartha; Natarajan, Pradeep; Silver, Alexander J.; Gibson, Christopher J.; Bick, Alexander G.; Shvartz, Eugenia; McConkey, Marie; Gupta, Namrata; Gabriel, Stacey (2017-06-21). "Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease". New England Journal of Medicine. 377 (2): 111–121. doi:10.1056/NEJMoa1701719. PMC 6717509. PMID 28636844.
  12. ^ Park, Soo J.; Bejar, Rafael (2020-03-01). "Clonal hematopoiesis in cancer". Experimental Hematology. 83: 105–112. doi:10.1016/j.exphem.2020.02.001. PMC 7103485. PMID 32044376.