b'u From Page 55progression to AML, MDS include a group of clonal3,000 patients with MDS assessed with a 95-gene hematopoietic disorders. Most cases have no indis- molecular profiling tool.putable cause or exposure and are considered deThe driver mutations identified in the AO cohort novo MDS. On the other hand, the authors of a 2020were similar to that seen in our control cohort and to study published in Blood noted that several causativethat seen in previously published sequencing stud-agents have been linked to the development of MDS,ies of MDS as well as our control cohort, including calledtherapy-relatedMDS,includingorganicrestricting the control cohort to males only and those solventssuchasbenzene,ionizingradiationandwith a similar age spectrum to the AO exposed popu-cytotoxic chemotherapy. lation, the authors pointed out. Thus, the spectrum In a 2020 article in Blood, Washington Universityof driver mutations seen in MDS exposed to AO is School of Medicine researchers estimated that aboutsimilar to that seen in de novo MDS.30% of MDS patients eventually progress to AML,NotingthatMDSisprimarilyadiseaseofthe which is diagnosed by an increase in blast countelderlywithmedianageatdiagnosisbetween to 20% of total nucleated cells in the bone marrow71-76, researchers advised that most of the muta-and is commonly termed secondary AML to MDS.tions they identified were consistent with the aging Secondary AML accounts for up to 25% to 35% ofrelated mutational signature that has been previously total AML cases, with most (60-80%) arising fromreported in MDS and acute myeloid leukemia.an antecedent MDS. 4 Insummary,herewereportthefirstdetailed TheDana-Farber-ledresearchersexplainedthatgenetic characterization of MDS in patients exposed Agent Orange (AO) was a phenoxy herbicide mix- to AO during the Vietnam War era. The landscape tureusedextensivelybytheUnitedStatesmili- of driver mutations and mutational events detected taryasastrategicdefoliant.Duringthe Vietnamin this population is similar to that seen in de novo War, when it was used the most, it was commonlyMDS and suggests that if AO promotes the develop-diluted in the field by military staff with kerosene,ment of MDS, it does so through a mechanism that gasoline or JP-4 jet fuel to facilitate aerosolizationis not associated with increased DNA damage, the and spraying from aircraft. authors concluded.While no clear link between the development ofThey cautioned, however, While we did not iden-MDS and exposure to AO has yet been documented,tify an association between any recurrently mutated the long latency for development and relative raritygenes or a clear mutational signature and AO expo-of MDS has made this difficult to assess in epide- sure, the limited size of this study does not exclude miological studies, and the potential hematopoieticthe possibility of an AO-induced carcinogenic pro-toxicity of AO has raised the possibility of an asso- cess that promotes the development of MDS.ciation, the authors wrote. 1Shallis RM, Gore SD. Agent Orange and dioxin-induced myeloid To determine if MDS that developed in AO-exposedleukemia: a weaponized vehicle of leukemogenesis. Leuk Lymphoma. individuals has a common etiologic link, research- 2022 Feb 2:1-10. doi: 10.1080/10428194.2022.2034156. Epub ahead ers performed next-generation exome sequencing toof print. PMID: 35105250.assess acquired somatic mutations in a panel of 292Khawandanah MO, Chaudry S, Morton J, Vidal G, et. al. Survival of Vietnam-era military veterans diagnosed with MDSacute myelogenous leukemia patients who served in the military com-pared to civilians. Journal of Clinical Oncology 2016 34:15_suppl, and who had prior reported exposure to AO that mete18524-e18524.the VA definition of presumptive AO exposure. 3Sperling AS, Leventhal M, Gibson CJ, Ebert BL, Steensma DP. Eligible veterans, who had a median age of 65 andMyelodysplastic syndromes (MDS) occurring in Agent Orange wereallwhitemales,wereaskedtocompleteanexposed individuals carry a mutational spectrum similar to that of online form and to provide a peripheral blood sam- de novo MDS. Leuk Lymphoma. 2020 Mar;61(3):728-731. doi: 10.1080/10428194.2019.1689394. Epub 2019 Nov 12. PMID: ple. Most of the 29 patients included in the study had31714164; PMCID: PMC7268906.served in the Army. In comparison, the study team4 Menssen AJ, Walter MJ. Genetics of progression from MDS to examined the exome sequences of nine patients withsecondary leukemia. Blood. 2020 Jul 2;136(1):50-60. doi: 10.1182/MDS without known military service or suspectedblood.2019000942. PMID: 32430504; PMCID: PMC7332895.AO exposure and also used a dataset of more than 62'