Abstract
The incidence of chronic myeloid leukemia (CML), which is caused by BCR/ABL chimeric oncogene formation in a pluripotent hematopoietic stem cell (HSC), increases with age and exposure to ionizing radiation. CML is a comparatively well-characterized neoplasm, important for its own sake and useful for insights into other neoplasms. Here, Surveillance, Epidemiology and End Results (SEER) CML data are analyzed after considering possible misclassification of chronic myelo-monocytic leukemia as CML. For people older than 25 years, plots of male and female CML log incidences versus age at diagnosis are approximately parallel straight lines with males either above or to the left of females. This is consistent with males having a higher risk of developing CML or a shorter latency from initiation to diagnosis of CML. These distinct mechanisms cannot be distinguished using SEER data alone. Therefore, CML risks among male and female Japanese A-bomb survivors are also analyzed. The present analyses suggest that sex differences in CML incidence more likely result from differences in risk than in latency. The simplest but not the sole interpretation of this is that males have more target cells at risk to develop CML. Comprehensive mathematical models of CML could lead to a better understanding of the role of HSCs in CML and other preleukemias that can progress to acute leukemia.
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Acknowledgments
We are very grateful to anonymous reviewers of the current and an earlier version of the manuscript for their thoughtful comments. TR, RKS and LH were supported by NCI ICBP U54CA149233. RKS was also supported by DOE DE-SC0001434 Office of Science (BER) US Department of Energy. TR and YS were supported by RO1CA138858. RPG acknowledges support from the NIHR Biomedical Research Centre funding scheme. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. GJ was supported by Grant # 41004 (Ministry of Science and Education, Republic of Serbia). RVT was supported by the Scott Hamilton CARES grant, Cleveland Clinic Seed Support and an ACS pilot grant. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE), the latter in part through DOE award DE-HS0000031 to the National Academy of Sciences. The conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies.
Conflict of interest
RPG is a part-time employee of Celgene Corp.
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Radivoyevitch, T., Jankovic, G.M., Tiu, R.V. et al. Sex differences in the incidence of chronic myeloid leukemia. Radiat Environ Biophys 53, 55–63 (2014). https://doi.org/10.1007/s00411-013-0507-4
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DOI: https://doi.org/10.1007/s00411-013-0507-4