Although acquired mutations in the GATA1 gene have been reported for Down syndrome-related acute megakaryoblastic leukemia (DS-AMKL) in Caucasians, this is the first report of a Korean Down syndrome patient with AMKL carrying a novel mutation of the GATA1 gene. A 3-yr-old Korean girl with Down syndrome was admitted to our hospital complaining of pallor and fever. The findings of a peripheral blood smear and bone marrow study were compatible with the presence of AMKL. A chromosome study showed 48,XX,-7,+21c,+21,+r[3]/47,XX,+21c[17]. Following GATA1 gene mutation analysis, a novel mutation, c.145dupG (p.Ala49GlyfsX18), was identified in the N-terminal activation domain of the GATA1 gene. This mutation caused a premature termination at codon 67 and expression of an abnormal GATA-1 protein with a defective N-terminal activation domain, and the absence of full-length GATA-1 protein. This case demonstrates that a leukemogenic mechanism for DS-AMKL is contributed by a unique collaboration between overexpressed genes from trisomy 21 and an acquired GATA1 mutation previously seen in Caucasians and now in a Korean patient.
Base Sequence ; Child, Preschool ; Chromosomes, Human, Pair 21 ; Down Syndrome/complications/diagnosis/*genetics ; Female ; GATA1 Transcription Factor/*genetics ; Humans ; Karyotyping ; Korea ; Leukemia, Megakaryoblastic, Acute/diagnosis/etiology/*genetics ; *Mutation ; Phenotype ; Trisomy

The association of hematological malignancies with a mediastinal germ cell tumor (GCT) is very rare. We report one case of a young adult male with primary mediastinal GCT who subsequently developed acute megakaryoblastic leukemia involving isochromosome (12p). A 25-yr-old man had been diagnosed with a mediastinal GCT and underwent surgical resection and adjuvant chemotherapy. At 1 week after the last cycle of chemotherapy, his peripheral blood showed leukocytosis with blasts. A bone marrow study confirmed the acute megakaryoblastic leukemia. A cytogenetic study revealed a complex karyotype with i(12p). Although additional chemotherapy was administered, the patient could not attain remission and died of septic shock. This case was definitely distinct from therapy-related secondary leukemia in terms of clinical, morphologic, and cytogenetic features. To our knowledge, this is the first case report of a patient with mediastinal GCT subsequently developing acute megakaryoblastic leukemia involving i(12p) in Korea.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bleomycin/administration & dosage ; Bone Marrow/pathology ; *Chromosomes, Human, Pair 12 ; Cisplatin/administration & dosage ; Etoposide/administration & dosage ; Humans ; Isochromosomes ; Karyotyping ; Leukemia, Megakaryoblastic, Acute/drug therapy/etiology/*genetics ; Male ; Mediastinal Neoplasms/*diagnosis/drug therapy/surgery ; Neoplasms, Germ Cell and Embryonal/*diagnosis/drug therapy/surgery ; Neoplasms, Second Primary/drug therapy/etiology/*genetics ; Republic of Korea ; Shock, Septic/pathology