Glanzmann thrombasthenia with acute myeloid leukemia successfully treated by bone marrow transplantation.

We report successful treatment by bone marrow transplantation (BMT) in an acute myeloid leukemia (AML) patient with Glanzmann thrombasthenia (GT). Genetic analysis revealed that a novel point mutation in exon 3 of the GPIIb gene led to abnormal splicing resulting in an amino acid substitution and an in-frame deletion of 3 amino acid residues. Expression studies suggested a rapid degradation of the uncomplexed protein within the cells.

Glanzmann thrombasthenia associated with a 21-amino acid deletion (Leu817-Gln837) in glycoprotein IIb due to abnormal splicing in exon 25.

We report a novel genetic defect in a Japanese patient with type I Glanzmann thrombasthenia. The glycoprotein (GP) Ilb complementary DNA (cDNA) from platelet messenger RNA had a 63-base pair deletion in the 5' boundary of exon 25, resulting in an in-frame deletion of 21 amino acid residues (Leu817-Gln837) in the calf-2 domain. The deleted region was present in the genomic DNA, but the splice acceptor site (AG) of exon 25 was mutated to AC, leading to the use of an AG sequence in the middle of exon 25 as an abnormal cryptic splice acceptor site.