Transient abnormal myelopoiesis in a Down syndrome newborn followed by acute myeloid leukemia: identification of the same chromosomal abnormality in both stages

A transient abnormal myelopoiesis was observed in a newborn with Down syndrome. Cytogenetic study revealed multiple oligoclonal abnormalities: 47,XY,inv(6)(p23q21),+21c[3]/47,XY,der(7)t(1;7)(q25;p15),+21c[1]/47,XY,del(13)(q?),+21c[1]/47,XY,+21c[15]. Ten months after the patient achieved remission, the transient abnormal myelopoiesis evolved to an acute megakaryoblastic leukemia. Cytogenetic study revealed only a single clonal abnormality, 47,XY,der(7)t(1;7)(q25;p15),+21c, identical to one of the structural changes seen at birth. Sequence analysis of the GATA1 gene revealed a deletion-insertion mutation within the exon 2 introducing a stop codon after Arg 64. It may be that the der(7)t(1;7)(q25;p15) abnormality played some selective role in the development of acute megakaryoblastic leukemia in this patient. To our knowledge, the present case is unique in demonstrating a subclone with der(7)t(1;7)(q25;p15) evolving to acute leukemia.