Chromosomal Analysis of Myelodysplastic Syndromes Among Atomic Bomb Survivors in Nagasaki

Abstract

[Background] Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that develop de novo and also secondary to chemotherapy and / or radiation therapy. We previously demonstrated that the risk of MDS is increased among atomic bomb survivors in Nagasaki, Japan with significant correlation to radiation dose (Iwanaga et al. JCO 2011). The latest our study showed that MDS among proximally radiated survivors to the hypocenter had higher frequency of chromosomal aberrations, especially those related to poor prognosis such as complex karyotypes, however, survival and leukemia transformation did not show statistical difference by the distance from hypocenter (Matsuo et al. Caner Sci 2016).[Aim] In this study, we investigated chromosomal abnormalities of MDS among survivors to address (1) whether specific chromosomal aberration exists, and (2) why karyotype did not have strong impact on the survival and leukemia transformation.[Methods] We collected clinical information of MDS patients diagnosed from 1985 to 2013 registered in the Nagasaki-City MDS database. This database includes information from five hospitals in Nagasaki city. Patients were diagnosed according to the French-American-British (FAB) classification criteria. Patient risk was evaluated using the International Prognostic Scoring System (IPSS), and the revised IPSS (IPSS-R).[Results and Discussion] There were 133 MDS patients among A-bomb survivors, and 269 were unexposed. Among survivors, the number of cases according to distance from the hypocenter was 29 in the <1.5km group (Group I), 35 in the 1.5-2.99 km group (Group II) and 69 in the ≥3 km group (Group III). Abnormal karyotype frequency was significantly higher with more very poor karyotypes, according to the revised International Prognostic Scoring System, among those exposed close to the hypocenter compared with unexposed cases. However, there was no difference in prognosis between exposed and unexposed cases. In the Group I, chromosomal translocations and inversions were more frequent, and the frequency of structural alterations in chromosomes 3, 8, and 11 was significantly increased compared with unexposed cases (P=0.007, 0.01, and 0.001, respectively). These results suggest that chromosomal alterations in MDS among survivors have different features compared with those in de novo or therapy-related MDS. Detailed molecular study is warranted. DisclosuresMiyazaki:Nippon Shinyaku: Honoraria. Haase:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.