Association of MLL amplification with poor outcome in acute myeloid leukemia

Chromosomal rearrangements and amplification of the MLL gene at 11q23 are common abnormalities found in patients with severe myelodysplastic disorders and lymphoid and acute myeloid leukemias. MLL rearrangements are associated with aggressive disease in both children and adults, with current evidence suggesting that MLL alterations are associated with a poor prognosis. We report the clinical, cytogenetic and histologic findings of a patient who presented with a de novo diagnosis of AML-M4 and who fits the profile of patients presenting with MLL alterations, such as old age at presentation, rapid progression, therapeutic refractoriness, and poor outcome. Two bone marrow specimens taken 1 month apart show the rapid deterioration of the patient's cytogenetic abnormalities at the 11q23 locus, with amplification of MLL that was originally seen as a homogeneously staining region (hsr) on chromosome 11. In the second biopsy the hsr and MLL amplification appears as nonreciprocal translocation of multiple copies in the form of marked amplification of MLL on chromosome 16 in a background of increasing chromosomal aberrations. This case suggests that either the MLL amplification and translocation alone or in conjunction with other flanking oncogenes may have played an important role in poor patient outcome.