Anticipation in familial hematologic malignancies

We describe a collection of 11 families with > 2 generations of family members whose condition has been diagnosed as a hematologic malignancy. In 9 of these families there was a significant decrease in age at diagnosis in each subsequent generation (anticipation). The mean age at diagnosis in the first generation was 67.8 years, 57.1 years in the second, and 41.8 years in the third (P < .0002). This was confirmed in both direct parentoffspring pairs with a mean reduction of 19 years in the age at diagnosis (P < .0087) and when the analysis was repeated only including cases of mature B-cell neoplasm (P < .0007). We believe that these families provide further insight into the nature of the underlying genetic mechanism of predisposition in these families.