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Acute Non Lymphocytic Leukemia

Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement

Abstract

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.

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Acknowledgements

We thank Dr Iou-Jih Hung, Dr Chao-Ping Yang and Dr Hung Chang for providing their patients’ samples. We also thank Ms Siew-Hoon Tech for the technical assistance, Ms Hsiu-I Wang for the statistical analysis and Ms Yu-Feng Wang for the secretarial assistance. This work was supported by NHRI-EX90-9011SL, NHRI-EX91-9011SL, NHRI-EX92-9011SL, NHRI-EX93-9011SL from the National Health Research Institute, Taiwan, Grant CMRP860 from Chang Gung Memorial Hospital, Taiwan, and Grant MMH-E-94009 from Mackay Memorial Hospital, Taiwan.

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Shih, Ly., Liang, Dc., Fu, Jf. et al. Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement. Leukemia 20, 218–223 (2006). https://doi.org/10.1038/sj.leu.2404024

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