Agent Orange and dioxin-induced myeloid leukemia: a weaponized vehicle of leukemogenesis

References

• Shallis RM, Ahmad R, Zeidan AM. The genetic and molecular pathogenesis of myelodysplastic syndromes. Eur J Haematol. 2018;101:260–271.
   PubMed Web of Science ®Google Scholar
• Shallis RM, Weiss JJ, Deziel NC, et al. Challenging the concept of de novo acute myeloid leukemia: environmental and occupational leukemogens hiding in our midst. Blood Rev. 2021;47:100760.
   PubMed Web of Science ®Google Scholar
• Wartiovaara-Kautto U, Hirvonen EAM, Pitkanen E, et al. Germline alterations in a consecutive series of acute myeloid leukemia. Leukemia. 2018;32:2282–2285.
   PubMed Web of Science ®Google Scholar
• Furutani E, Shimamura A. Genetic predisposition to MDS: diagnosis and management. Hematol Am Soc Hematol Educ Program. 2019;2019(1):110–119.
   PubMedGoogle Scholar
• Shlush LI, Zandi S, Mitchell A, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506:328–333.
   PubMed Web of Science ®Google Scholar
• Corces-Zimmerman MR, Hong WJ, Weissman IL, et al. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A. 2014;111:2548–2553.
   PubMed Web of Science ®Google Scholar
• Korn C, Mendez-Ferrer S. Myeloid malignancies and the microenvironment. Blood. 2017;129:811–822.
   PubMed Web of Science ®Google Scholar
• Shallis RM, Wang R, Davidoff A, et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Shallis RM, Wang R, et al. Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev. 2019;34:1–15.
   PubMed Web of Science ®Google Scholar
• Ma X, Lim U, Park Y, et al. Obesity, lifestyle factors, and risk of myelodysplastic syndromes in a large US cohort. Am J Epidemiol. 2009;169(12):1492–1499.
   PubMed Web of Science ®Google Scholar
• Li S, Chen L, Jin W, et al. Influence of body mass index on incidence and prognosis of acute myeloid leukemia and acute promyelocytic leukemia: a Meta-analysis. Sci Rep. 2017;7:17998.
   PubMed Web of Science ®Google Scholar
• Poynter JN, Richardson M, Blair CK, et al. Obesity over the life course and risk of acute myeloid leukemia and myelodysplastic syndromes. Cancer Epidemiol. 2016;40:134–140.
   PubMed Web of Science ®Google Scholar
• Strom SS, Oum R, Elhor Gbito KY, et al. De novo acute myeloid leukemia risk factors: a Texas case-control study. Cancer. 2012;118:4589–4596.
   PubMed Web of Science ®Google Scholar
• Du Y, Fryzek J, Sekeres MA, et al. Smoking and alcohol intake as risk factors for myelodysplastic syndromes (MDS). Leuk Res. 2010;34:1–5.
   PubMed Web of Science ®Google Scholar
• Strom SS, Gu Y, Gruschkus SK, et al. Risk factors of myelodysplastic syndromes: a case-control study. Leukemia. 2005;19:1912–1918.
   PubMed Web of Science ®Google Scholar
• Nisse C, Haguenoer JM, Grandbastien B, et al. Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France. Br J Haematol. 2001;112:927–935.
   PubMed Web of Science ®Google Scholar
• Lv L, Lin G, Gao X, et al. Case-control study of risk factors of myelodysplastic syndromes according to world health organization classification in a Chinese population. Am J Hematol. 2011;86:163–169.
   PubMed Web of Science ®Google Scholar
• Dalamaga M, Petridou E, Cook FE, et al. Risk factors for myelodysplastic syndromes: a case-control study in Greece. Cancer Causes Control. 2002;13:603–608.
   PubMed Web of Science ®Google Scholar
• Bjork J, Johansson B, Broberg K, et al. Smoking as a risk factor for myelodysplastic syndromes and acute myeloid leukemia and its relation to cytogenetic findings: a case-control study. Leuk Res. 2009;33:788–791.
   PubMed Web of Science ®Google Scholar
• Fircanis S, Merriam P, Khan N, et al. The relation between cigarette smoking and risk of acute myeloid leukemia: an updated meta-analysis of epidemiological studies. Am J Hematol. 2014;89(8):E125–32.
   PubMed Web of Science ®Google Scholar
• Lichtman MA. Cigarette smoking, cytogenetic abnormalities, and acute myelogenous leukemia. Leukemia. 2007;21:1137–1140.
   PubMed Web of Science ®Google Scholar
• Hamner CL, Tukey HB. The herbicidal action of 2,4 dichlorophenoxyacetic and 2,4,5 trichlorophenoxyacetic acid on bindweed. Science. 1944;100:154–155.
   PubMedGoogle Scholar
• Mullison WR. The relative herbicidal effectiveness of several derivatives of 2,4-Dichlorophenoxyacetic acid and 2,4,5-Trichlorophenoxyacetic acid. Plant Physiol. 1951;26:773–777.
   PubMed Web of Science ®Google Scholar
• Veterans and Agent Orange: update 11. Washington (DC): National Academies of Sciences, Engineering, and Medicine; 2018.
   Google Scholar
• Stellman JM, Stellman SD. Agent Orange during the Vietnam war: the lingering issue of its civilian and military health impact. Am J Public Health. 2018;108:726–728.
   PubMed Web of Science ®Google Scholar
• Stellman JM, Stellman SD, Christian R, et al. The extent and patterns of usage of Agent Orange and other herbicides in Vietnam. Nature. 2003;422:681–687.
   PubMed Web of Science ®Google Scholar
• Sperling AS, Leventhal M, Gibson CJ, et al. Myelodysplastic syndromes (MDS) occurring in Agent Orange exposed individuals carry a mutational spectrum similar to that of de novo MDS. Leuk Lymphoma. 2020;61:728–731.
   PubMed Web of Science ®Google Scholar
• Courtney KD, Gaylor DW, Hogan MD, et al. Teratogenic evaluation of 2,4,5-T. Science. 1970;168:864–866.
   PubMed Web of Science ®Google Scholar
• Courtney KD, Moore JA. Teratology studies with 2,4,5-trichlorophenoxyacetic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1971;20:396–403.
   PubMed Web of Science ®Google Scholar
• IARC working group on the evaluation of carcinogenic risks to humans: polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans. Lyon, France, 4–11 February 1997. IARC Monogr Eval Carcinog Risks Hum 69:1–631. 1997.
   Google Scholar
• Pesatori AC, Consonni D, Rubagotti M, et al. Cancer incidence in the population exposed to dioxin after the "Seveso accident": twenty years of follow-up. Environ Health. 2009;8:39.
   PubMed Web of Science ®Google Scholar
• Bertazzi PA, Zocchetti C, Pesatori AC, et al. Ten-year mortality study of the population involved in the Seveso incident in 1976. Am J Epidemiol. 1989;129:1187–1200.
   PubMed Web of Science ®Google Scholar
• Bertazzi PA, Consonni D, Bachetti S, et al. Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol. 2001;153:1031–1044.
   PubMed Web of Science ®Google Scholar
• Ramlow JM, Spadacene NW, Hoag SR, et al. Mortality in a cohort of pentachlorophenol manufacturing workers, 1940-1989. Am J Ind Med. 1996;30(2):180–194.
   PubMed Web of Science ®Google Scholar
• Hardell L, Sandstrom A. Case-control study: soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols. Br J Cancer. 1979;39:711–717.
   PubMed Web of Science ®Google Scholar
• Kogevinas M, Kauppinen T, Winkelmann R, et al. Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies. Epidemiology. 1995;6:396–402.
   PubMed Web of Science ®Google Scholar
• Steenland K, Piacitelli L, Deddens J, et al. Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Natl Cancer Inst. 1999;91:779–786.
   PubMed Web of Science ®Google Scholar
• Hooiveld M, Heederik DJ, Kogevinas M, et al. Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides, chlorophenols, and contaminants. Am J Epidemiol. 1998;147:891–901.
   PubMed Web of Science ®Google Scholar
• Boers D, Portengen L, Bueno-de-Mesquita HB, et al. Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing workers. Occup Environ Med. 2010;67:24–31.
   PubMed Web of Science ®Google Scholar
• Becher H, Flesch-Janys D, Kauppinen T, et al. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins. Cancer Causes Control. 1996;7:312–321.
   PubMed Web of Science ®Google Scholar
• Flesch-Janys D, Steindorf K, Gurn P, et al. Estimation of the cumulated exposure to polychlorinated dibenzo-p-dioxins/furans and standardized mortality ratio analysis of cancer mortality by dose in an occupationally exposed cohort. Environ Health Perspect. 1998;106(Suppl 2):655–662.
   PubMed Web of Science ®Google Scholar
• Rix BA, Villadsen E, Engholm G, et al. Hodgkin's disease, pharyngeal cancer, and soft tissue sarcomas in Danish paper mill workers. J Occup Environ Med. 1998;40:55–62.
   PubMed Web of Science ®Google Scholar
• McLean D, Pearce N, Langseth H, et al. Cancer mortality in workers exposed to organochlorine compounds in the pulp and paper industry: an international collaborative study. Environ Health Perspect. 2006;114:1007–1012.
   PubMed Web of Science ®Google Scholar
• Wigle DT, Semenciw RM, Wilkins K, et al. Mortality study of Canadian male farm operators: non-Hodgkin's lymphoma mortality and agricultural practices in Saskatchewan. J Natl Cancer Inst. 1990;82:575–582.
   PubMed Web of Science ®Google Scholar
• Morrison HI, Semenciw RM, Wilkins K, et al. Non-Hodgkin's lymphoma and agricultural practices in the prairie provinces of Canada. Scand J Work Environ Health. 1994;20:42–47.
   PubMed Web of Science ®Google Scholar
• Consonni D, Pesatori AC, Zocchetti C, et al. Mortality in a population exposed to dioxin after the Seveso, Italy, accident in 1976: 25 years of follow-up. Am J Epidemiol. 2008;167:847–858.
   PubMed Web of Science ®Google Scholar
• Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33:451–458.
   PubMed Web of Science ®Google Scholar
• Saarni MI, Linman JW. Preleukemia. The hematologic syndrome preceding acute leukemia. Am J Med. 1973;55:38–48.
   PubMed Web of Science ®Google Scholar
• Jaffe ES, Harris NL, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon (France): IARC; 2001.
   Google Scholar
• Hill AB: the environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300.
   PubMed Web of Science ®Google Scholar
• Gross ML, Lay JO, Jr., Lyon PA, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of Vietnam veterans. Environ Res. 1984;33:261–268.
   PubMed Web of Science ®Google Scholar
• Kahn PC, Gochfeld M, Nygren M, et al. Dioxins and dibenzofurans in blood and adipose tissue of agent orange-exposed Vietnam veterans and matched controls. JAMA. 1988;259:1661–1667.
   PubMed Web of Science ®Google Scholar
• Kang HK, Watanabe KK, Breen J, et al. Dioxins and dibenzofurans in adipose tissue of US vietnam veterans and controls. Am J Public Health. 1991;81:344–349.
   PubMed Web of Science ®Google Scholar
• Pirkle JL, Wolfe WH, Patterson DG, et al. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of operation ranch hand. J Toxicol Environ Health. 1989;27:165–171.
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in air force health study participants–preliminary report. MMWR Morb Mortal Wkly Rep. 1988;37:309–311.
   PubMedGoogle Scholar
• Sakata R, Grant EJ, Ozasa K. Long-term follow-up of atomic bomb survivors. Maturitas. 2012;72:99–103.
   PubMed Web of Science ®Google Scholar
• Tsushima H, Iwanaga M, Miyazaki Y. Late effect of atomic bomb radiation on myeloid disorders: leukemia and myelodysplastic syndromes. Int J Hematol. 2012;95:232–238.
   PubMed Web of Science ®Google Scholar
• Iwanaga M, Hsu WL, Soda M, et al. Risk of myelodysplastic syndromes in people exposed to ionizing radiation: a retrospective cohort study of Nagasaki atomic bomb survivors. J Clin Oncol. 2011;29(4):428–434.
   PubMed Web of Science ®Google Scholar
• Williams Z, Hardy SJ, Berger C, et al. Driver mutation acquisition in utero and childhood followed by lifelong clonal evolution underlie myeloproliferative neoplasms. Blood. 2020;136(Supplement 1):11–11.
   PubMedGoogle Scholar
• Poland A, Glover E, Kende AS. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem. 1976;251:4936–4946.
   PubMed Web of Science ®Google Scholar
• Whitlock JP. Jr. Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol. 1999;39:103–125.
   PubMed Web of Science ®Google Scholar
• Kurachi M, Hashimoto S, Obata A, et al. Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression. Biochem Biophys Res Commun. 2002;292(2):368–377.
   PubMed Web of Science ®Google Scholar
• Mimura J, Fujii-Kuriyama Y. Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta. 2003;1619:263–268.
   PubMed Web of Science ®Google Scholar
• Teino I, Matvere A, Pook M, et al. Impact of AHR ligand TCDD on human embryonic stem cells and early differentiation. Int J Mol Sci. 2020;21(23):9052.
   PubMed Web of Science ®Google Scholar
• Lindsey S, Papoutsakis ET. The evolving role of the aryl hydrocarbon receptor (AHR) in the normophysiology of hematopoiesis. Stem Cell Rev Rep. 2012;8:1223–1235.
   PubMed Web of Science ®Google Scholar
• Angelos MG, Ruh PN, Webber BR, et al. Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells. Blood. 2017;129:3428–3439.
   PubMed Web of Science ®Google Scholar
• Ly M, Rentas S, Vujovic A, et al. Diminished AHR signaling drives human acute myeloid leukemia stem cell maintenance. Cancer Res. 2019;79:5799–5811.
   PubMed Web of Science ®Google Scholar
• Seaton MJ, Schlosser PM, Bond JA, et al. Benzene metabolism by human liver microsomes in relation to cytochrome P450 2E1 activity. Carcinogenesis. 1994;15:1799–1806.
   PubMed Web of Science ®Google Scholar
• Nedelcheva V, Gut I, Soucek P, et al. Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression. Arch Toxicol. 1999;73:33–40.
   PubMed Web of Science ®Google Scholar
• Rappaport SM, Waidyanatha S, Qu Q, et al. Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism. Cancer Res. 2002;62:1330–1337.
   PubMed Web of Science ®Google Scholar
• Rappaport SM, Waidyanatha S, Yeowell-O'Connell K, et al. Protein adducts as biomarkers of human benzene metabolism. Chem Biol Interact. 2005;153-154:103–109.
   PubMed Web of Science ®Google Scholar
• Smith MT, Zhang L, Jeng M, et al. Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells. Carcinogenesis. 2000;21(8):1485–1490.
   PubMed Web of Science ®Google Scholar
• Stillman WS, Varella-Garcia M, Irons RD. The benzene metabolite, hydroquinone, selectively induces 5q31- and -7 in human CD34 + CD19-bone marrow cells. Exp Hematol. 2000;28:169–176.
   PubMed Web of Science ®Google Scholar
• Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon (France): IARC; 2017.
   Google Scholar
• Ji Z, Zhang L, Peng V, et al. A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide. Leukemia. 2010;24:986–991.
   PubMed Web of Science ®Google Scholar
• Ren J, Cui JP, Luo M, et al. The prevalence and persistence of aberrant promoter DNA methylation in benzene-exposed Chinese workers. PLoS One. 2019;14(8):e0220500.
   PubMed Web of Science ®Google Scholar
• Shallis RM, Weiss JJ, Deziel NC, et al. A clandestine culprit with critical consequences: benzene and acute myeloid leukemia. Blood Rev. 2020;47:100736.
   PubMed Web of Science ®Google Scholar
• Linet MS, Gilbert ES, Vermeulen R, et al. Benzene exposure response and risk of myeloid neoplasms in Chinese workers: a multicenter case-cohort study. J Natl Cancer Inst. 2019;111(5):465–474.
   PubMedGoogle Scholar
• U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry. ATSDR assessment of the evidence for the drinking water contaminants at camp lejeune and specific cancers and other diseases. 2017. https://www.atsdr.cdc.gov/sites/peer_review/camp_lejeune.html
   Google Scholar
• Bertazzi PA, Pesatori AC, Bernucci I, et al. Dioxin exposure and human leukemias and lymphomas. Lessons from the Seveso accident and studies on industrial workers. Leukemia. 1999;13(Suppl 1):S72–S74.
   PubMedGoogle Scholar
• Pesatori AC, Consonni D, Tironi A, et al. Cancer in a young population in a dioxin-contaminated area. Int J Epidemiol. 1993;22:1010–1013.
   PubMed Web of Science ®Google Scholar
• Bertazzi PA, Zocchetti C, Guercilena S, et al. Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident". Epidemiology. 1997;8:646–652.
   PubMed Web of Science ®Google Scholar
• Collins JJ, Bodner KM, Wilken M, et al. Serum concentrations of chlorinated dibenzo-p-dioxins and dibenzofurans among former Michigan trichlorophenol and pentachlorophenol workers. J Expo Sci Environ Epidemiol. 2007;17:541–548.
   PubMed Web of Science ®Google Scholar
• Collins JJ, Bodner KM, Aylward LL, et al. Mortality risk among workers with exposure to dioxins. Occup Med. 2016;66:706–712.
   Google Scholar
• Kogevinas M, Becher H, Benn T, et al. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. Am J Epidemiol. 1997;145:1061–1075.
   PubMed Web of Science ®Google Scholar
• Zober A, Messerer P, Huber P. Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident. Int Arch Occup Environ Health. 1990;62:139–157.
   PubMed Web of Science ®Google Scholar