Dietary flavonoids and the MLL gene: A pathway to infant leukemia?

Infant leukemia, diagnosed in the first 12 months of life, is extremely rare in the United States; the overall annual incidence is estimated to be approximately 37 cases per million infants (1). Certain demographic information with respect to incidence may provide important clues regarding etiology. White infants experience about a 50% higher risk than black infants, and females about a 50% higher risk than males (1). The observation of a higher risk in infant females is particularly notable given the overall higher risk of leukemia (≈30%) in male children under the age of 15 as compared with female children (2). With the exception of in utero exposure to radiation and prior chemotherapy treatments, little is known about the causes of childhood leukemia (reviewed in ref. 2). This paucity of information is likely attributable largely to the heterogeneity of the disease and to insufficient study power to test hypotheses within more homogenous subgroups. In particular, age at diagnosis and/or biologically distinct subgroups are likely reflective of different etiologic mechanisms. Several epidemiologic studies have observed specific risk factors that are fairly consistently associated with younger children who develop leukemia (reviewed in refs. 2 and 3). These include (i) a birth weight in excess of 4,000 g [a 2-fold increased risk associated with both acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) in children under the age of 2]; (ii) maternal alcohol consumption during pregnancy (a 1.5-fold increased risk associated with infant AML); and (iii) maternal history of miscarriage or stillbirth (2- to 5-fold excess risks of infant AML and ALL). Biologically, infant leukemias represent a distinct group for the epidemiologic study of hematopoietic neoplasms. The majority of infant cases (including about 80% of infants with ALL and 65% of infants with AML) have rearrangements involving the MLL gene on chromosome …