Hematopoyesis Clonal de Potencial Indeterminado (HCPI): más allá de un modelo de campo de cancerización

  • Oscar Andres Franco Tavera Universidad Nacional de Colombia
  • Natalia Olaya Morales
Palabras clave: Hematopoyesis clona, expansión clonal, campo de cancerización, quimioterapia, Neoplasia Mieloide asociada a terapia, mutación somática, inflamación, envejecimiento

Resumen

La Hematopoyesis Clonal de Potencial Indeterminado (HCPI) más conocido como CHIP por sus siglas en ingles se define como la expansión clonal de Células Madre Hematopoyéticas (CMHs) que albergan una o más mutaciones somáticas (en la mayoría de los casos una sola mutación) sin un cáncer hematológico subyacente ni evidencia morfológica definitiva de displasia, con una frecuencia alélica mayor al 2%. Los individuos con HCPI progresan a malignidad a una tasa de cerca del 0.5 a 1% por año, convirtiéndose así en un modelo de campo de cancerización. Sin embargo, sus implicaciones van más allá debido a que se ha encontrado asociación con enfermedades inflamatorias crónicas como enfermedad cardiovascular ateroesclerótica, diabetes y enfermedades autoinmunes. Además, es considerado un factor predictivo en pacientes con cáncer hematolológico y no hematológico que reciben quimioterapia y radioterapia. 

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Referencias

Greaves M. Does everyone develop covert cancer? Nat Rev Cancer. 2014;14(4):209-10. doi: 10.1038/nrc3703.

United Nations. Department of Economic and Social Affairs. Population Division. World population ageing, 1950-2050. New York: United Nations; 2002.

Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758-65. doi: 10.1200/JCO.2008.20.8983.

Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science. 2019;366(6465). doi: 10.1126/science.aan4673.

Curtius K, Wright NA, Graham TA. An evolutionary perspective on field cancerization. Nat Rev Cancer. 2018;18(1):19-32. doi: 10.1038/nrc.2017.102.

Tomasetti C, Li L, Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355(6331):1330-1334. doi:10.1126/science.aaf9011

Ståhl PL, Stranneheim H, Asplund A, Berglund L, Pontén F, Lundeberg J. Sun-induced nonsynonymous p53 mutations are extensively accumulated and tolerated in normal appearing human skin. J Invest Dermatol. 2011;131(2):504-8. doi:10.1038/jid.2010.302.

Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150(2):264-78. doi: 10.1016/j.cell.2012.06.023.

Silver AJ, Jaiswal S. Clonal hematopoiesis: Pre-cancer PLUS. Adv Cancer Res. 2019;141:85-128. doi: 10.1016/bs.acr.2018.12.003.

Duncavage EJ, Tandon B. The utility of next-generation sequencing in diagnosis and monitoring of acute myeloid leukemia and myelodysplastic syndromes. Int J Lab Hematol. 2015;37 Suppl 1:115-21. doi: 10.1111/ijlh.12361.

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(8):1239-45. doi: 10.1016/j.celrep.2015.02.005.

Park SJ, Bejar R. Clonal hematopoiesis in cancer. Exp Hematol. 2020;83:105-112. doi: 10.1016/j.exphem.2020.02.001.

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(12):1472-8. doi: 10.1038/nm.3733.

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 25;371(26):2488-98. doi: 10.1056/NEJMoa1408617.

Genovese G, Kähler 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(26):2477-87. doi: 10.1056/NEJMoa1409405.

Young AL, Challen GA, Birmann BM, Druley TE. Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nat Commun. 2016;7:12484. doi: 10.1038/ncomms12484.

Duncan BK, Miller JH. Mutagenic deamination of cytosine residues in DNA. Nature. 1980;287(5782):560-1.

Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, et al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther. 2019;4:62. doi: 10.1038/s41392-019-0095-0.

Grinfeld J, Nangalia J, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R, et al. Classification and Personalized Prognosis in Myeloproliferative Neoplasms. N Engl J Med. 2018;379(15):1416-1430. doi:10.1056/NEJMoa1716614.

Chen S, Wang Q, Yu H, Capitano ML, Vemula S, Nabinger SC, et al. Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway. Nat Commun. 2019;10(1):5649. doi: 10.1038/s41467-019-13542-2.

Lee M, Dragoljevic D, Bertuzzo C, Wang N, Yvan-Charvert L, Murphy A. Interplay between Clonal Hematopoiesis of Indeterminate Potential and Metabolism. Trends Endocrinol Metab. 2020. doi: 10.1016/j.tem.2020.02.005.

Gibson CJ, Lindsley RC, Tchekmedyian V, Mar BG, Shi J, Jaiswal S, et al. Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma. J Clin Oncol. 2017;35(14):1598-1605. doi: 10.1200/JCO.2016.71.6712.

Hsu JI, Dayaram T, Tovy A, De Braekeleer E, Jeong M, Wang F, et al. PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy. Cell Stem Cell. 2018;23(5):700-713.e6. doi: 10.1016/j.stem.2018.10.004.

Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-90. doi: 10.1056/NEJMoa051113.

Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11-24. doi: 10.1016/j.ccr.2011.06.001.

Challen GA, Sun D, Jeong M, Luo M, Jelinek J, Berg JS, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet. 2011;44(1):23-31. doi: 10.1038/ng.1009.

Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496-506. doi: 10.1056/NEJMoa1013343.

Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886.

Devillier R, Gelsi-Boyer V, Brecqueville M, Carbuccia N, Murati A, Vey N, et al. Acute myeloid leukemia with myelodysplasia-related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations. Am J Hematol. 2012;87(7):659-62. doi: 10.1002/ajh.23211.

Cancer Genome Atlas Research Network, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-74. doi: 10.1056/NEJMoa1301689.

Steensma D, Bejar R, Jaiswal S, Lindsley C, Sekeres M, Hasserjian R, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9-16. doi: 10.1182/blood-2015-03-631747.

Desai P, Mencia-Trinchant N, Savenkov O, Simon MS, Cheang G, Lee S, et al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat Med. 2018;24(7):1015-1023. doi: 10.1038/s41591-018-0081-z.

Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, Niemeyer E, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559(7714):400-404. doi: 10.1038/s41586-018-0317-6.

Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, Jonsson P, et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell. 2017;21(3):374-382.e4. doi: 10.1016/j.stem.2017.07.010.

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(7540):552-555. doi: 10.1038/nature13968.

Boucai L, Falcone J, Ukena J, Coombs CC, Zehir A, Ptashkin R, et al. Radioactive Iodine-Related Clonal Hematopoiesis in Thyroid Cancer Is Common and Associated With Decreased Survival. J Clin Endocrinol Metab. 2018;103(11):4216-4223. doi: 10.1210/jc.2018-00803.

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;130(6):742‐752. doi:10.1182/blood-2017-02-769869

Murphy AJ, Tall AR. Disordered haematopoiesis and athero-thrombosis. Eur Heart J. 2016;37(14):1113-21. doi: 10.1093/eurheartj/ehv718

Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017;377(2):111-121. doi: 10.1056/NEJMoa1701719.

Cook EK, Izukawa T, Young S, Rosen G, Jamali M, Zhang L, et al. Comorbid and inflammatory characteristics of genetic subtypes of clonal hematopoiesis. Blood Adv. 2019;3(16):2482-2486. doi: 10.1182/bloodadvances.2018024729.

Arends CM, Galan-Sousa J, Hoyer K, Chan W, Jäger M, Yoshida K, et al. Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. Leukemia. 2018;32(9):1908-1919. doi: 10.1038/s41375-018-0047-7.

Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature. 2015;525(7569):389-393. doi: 10.1038/nature15252.

Moldogazieva NT, Mokhosoev IM, Terentiev AA. Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK. Cancers (Basel). 2020;12(4). doi: 10.3390/cancers12040862.

Wu D, Hu D, Chen H, Shi G, Fetahu IS, Wu F, et al. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature. 2018;559(7715):637-641. doi: 10.1038/s41586-018-0350-5.

Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19(1):17-30. doi: 10.1016/j.ccr.2010.12.014.

Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1:S4-9. doi: 10.1093/gerona/glu057.

Cook EK, Luo M, Rauh MJ. Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity. Exp Hematol. 2020;83:85-94. doi: 10.1016/j.exphem.2020.01.011.

Babushok DV, Olson TS, Bessler M. Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia. N Engl J Med. 2015; 373(17): 1673. doi: 10.1056/NEJMc1509703#SA1

Murakami Y, Kosaka H, Maeda Y, Nishimura J, Inoue N, Ohishi K, et al. Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuria. Blood. 2002;100(12):4116-22.

Savola P, Lundgren S, Keränen MAI, Almusa H, Ellonen P, Leirisalo-Repo M, et al. Clonal hematopoiesis in patients with rheumatoid arthritis. Blood Cancer J. 2018;8(8):69. doi: 10.1038/s41408-018-0107-2.

Publicado
2021-05-06
Cómo citar
[1]
Franco Tavera, O.A. y Olaya Morales, N. 2021. Hematopoyesis Clonal de Potencial Indeterminado (HCPI): más allá de un modelo de campo de cancerización. Revista Colombiana de Cancerología. 25, 4 (may 2021), 210-221. DOI:https://doi.org/10.35509/01239015.726.
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