FAMILIAL MYELOID-LEUKEMIA ASSOCIATED WITH LOSS OF THE LONG ARM OF CHROMOSOME-5

A 24-member kindred is described in which four cases of acute myeloid leukemia (AML), and one case of myelodysplastic syndrome (MDS) occurre d over three generations. The proband was diagnosed with AML at age 47 ; within 6 months, her sister, age 41, was diagnosed with MDS. The pro band's father, grandfather and a paternal uncle all died of AML, prece ded by a preleukemic phase. The five cases had several clinical featur es in common. In the two sisters and their paternal uncle, cyto-geneti c analyses of bone marrow cells revealed a common abnormality characte rized by loss of the long arm of chromosome 5, del(5q). No constitutio nal cytogenetic abnormality was detected in mitogen-stimulated periphe ral blood lymphocytes from the proband, In addition, there was no hist ory of common environmental or occupational exposure in the family. Th e occurrence of AML and MDS in three generations of this family most l ikely resulted from a single gene defect with an autosomal dominant pa ttern of inheritance. The association with the somatic loss of 5q mate rial in the leukemia cells of affected members suggests that a germlin e mutation of a leukemia suppressor gene located on 5q might be the pr imary event responsible for hereditary susceptibility to leukemia in t his family.