The study of cancer predisposition syndromes leads to identification and understanding of mutations in genes coding for proteins and cellular pathways leading to cancer development, as well as normal cell growth and death regulators. Many patients with cancer predisposition syndromes experience excess toxicity with standard therapeutic regimens and are at lifelong risk for development of additional cancers and must be followed closely; early diagnosis is crucial for appropriate management of these patients. This review describes specific leukemia-predisposing conditions, including the clinical and historical findings that should trigger testing for these syndromes, and discusses recent insights into the management of these disorders. Disorders are organized by mechanism: (1) DNA damage repair defects, including Fanconi anemia, ataxia-telangiectasia, Nijmegen breakage syndrome, and Bloom syndrome; (2) cell cycle and differentiation defects, such as neurofibromatosis type 1, Noonan and Noonan-like syndromes, and severe congenital neutropenia; (3) the hereditary transcription factor syndromes familial platelet disorder with predisposition to myeloid malignancy and CEBPA deficiency; and (4) aneuploidy-associated leukemia predisposition, exemplified by Down syndrome. Identifying the specific mechanisms underlying these relatively rare conditions allows for better understanding of leukemogenesis and development of targeted therapies that benefit a much broader population than simply those with genetic predispositions to leukemia.
2011 Elsevier Inc. All rights reserved.