Prevalence and Clinical Implication of Partial Tandem Duplication of the Mixed Lineage Leukemia Gene in Pediatric Acute Leukemia

Background: The mixed lineage leukemia (MLL) gene may induce hematopoiesis and leukemia. Partial tandem duplication of MLL (MLL-PTD) is associated with poor prog-nosis in acute myeloid leukemia (AML); however, the significance of MLL-PTD in acute lymphoblastic leukemia (ALL) has not been thoroughly studied. We evaluated the in-cidence, relationship with other cytogenetic abnormalities, and the prognostic role of MLL-PTD in ALL.Methods: We reviewed medical records from pediatric patients diagnosed with ALL in Severance Hospital, Yonsei University Health System, South Korea from 2002 to 2008. MLL-PTD was detected by nested reverse transcriptase polymerase chain reaction.Results: In ALL patients, 50.0% (42/84) were positive for MLL-PTD. There was no sig-nificant difference in the 10-year overall survival (10Y OS) and event-free survival (EFS) between MLL-PTD-positive (+) and MLL-PTD-negative (–) groups (69.4% vs. 76.2%, P=0.609, and 62.6% vs. 66.7%, P=0.818, respectively). The combination of high level of lactate dehydrogenase (＞1,100 IU/L) and MLL-PTD(+) [MLL-PTD(+)/High LDH] was a statistically significant negative prognostic factor for 10Y OS and EFS (P=0.0226 and P=0.0230, respectively). In multivariate analysis, National Cancer Institute risk strat-ification and very high risk features were independent significant prognostic factors but MLL-PTD (+)/High LDH was not.Conclusion: MLL-PTD was observed frequently in pediatric ALL patients. MLL-PTD was not an independent prognostic factor. MLL-PTD (+)/High LDH should be evaluated fur-ther for its prognostic potential in ALL.ope