Review of the cytogenetic changes in acute megakaryoblastic leukemia: one disease or several?

The karyotypes of 116 cases of acute megakaryoblastic leukemia (AMKL) were reviewed, including 43 pediatric patients with Down syndrome (DS) and 73 non-DS patients. DS patients with AMKL often had a history of transient leukemia or myelodysplasia with an early age of onset of AMKL (median 23 months). In these patients, the frequency of additional cytogenetic change (numerical or structural) was low, with 10 of the 43 DS patients showing no additional cytogenetic change. A second group of patients had t(1;22)(p13;q13) or other cytogenetic abnormality involving 22q13. These patients had no history of transient leukemia but showed very early onset of AMKL. In this group of patients, marked organomegaly was noted; these patients also showed few specific additional cytogenetic changes. The remaining AMKL patients had a median age of 30 years with much more frequent cytogenetic changes, including rearrangement of 3q21 and 3q26-27, trisomy 21, and other specific changes. Based on the karyotype and clinical data, we hypothesize that AMKL may represent at least three separate disease entities with different genetic alterations giving rise to similar, but not identical, disorders. Subclassification of AMKL on the basis of the cytogenetic changes in the leukemic cells appears to be justified.