Tandem duplication of the MLL gene in myelodysplastic syndrome-derived overt leukemia with trisomy 11.

Trisomy 11 as a sole chromosomal abnormality is a rare aberration observed in myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML). Recently a partial tandem duplication of the MLL gene, located on chromosome band 11q23, has been identified in de novo AML with trisomy 11. We describe a 72-year-old woman suffering from MDS-derived overt leukemia with trisomy 11 and a tandem duplication of the MLL gene. At first the patient was found to have myeloblasts with Auer rods in the peripheral blood and diagnosed as MDS, refractory anemia with excess of blasts in transformation (RAEB-T). After 2 months a picture of overt leukemia (AML; M2) developed as shown by an increased number of myeloblasts. Various chemotherapy regimens had little effect, and she died of disease progression 15 months after admission. During her clinical course, the chromosome analyses consistently showed 47,XX, +11. Southern blot analysis of leukemic blasts on admission and in accelerated phase revealed identical rearranged bands of the MLL gene. Fluorescence in situ hybridization analysis excluded the possibility of masked translocation of the MLL gene to other chromosomes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using a forward exon 6 primer and a backward exon 3 primer demonstrated an in-frame fusion of exon 8 with exon 2. Our results indicated that a partial tandem duplication of exons 2-8 of the MLL gene could be observed in MDS-derived overt leukemia as well as de novo AML with trisomy 11.