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  • Title: FISH analysis of MLL gene rearrangements: detection of the concurrent loss or gain of the 3' signal and its prognostic significance.
    Author: Lim JH, Jang S, Park CJ, Chi HS, Lee JO, Seo EJ.
    Journal: Int J Lab Hematol; 2014 Oct; 36(5):571-9. PubMed ID: 24612538.
    Abstract:
    INTRODUCTION: The rearrangement of the mixed-lineage leukemia (MLL) gene occurs through translocations and insertions involving a variety of partner chromosome genes. However, there are few studies on aberrant MLL signal patterns such as concurrent 3' MLL deletion. METHODS: A total of 84 patients with acute leukemia (AL) who had MLL rearrangements detected by florescence in situ hybridization (FISH) were enrolled in the study. The distribution of MLL fusion partner genes was analyzed, and aberrant MLL signals were evaluated. RESULTS: Seventy-seven (91.7%) patients had MLL rearrangements, involving previously described translocation partner genes (TPGs). Among these TPGs, the frequencies of MLLT3, AFF1, MLLT4, and ELL were 29.8%, 17.9%, 15.5%, and 13.1%, respectively. A high frequency of MLLT4 in our study was due to the high proportion of acute myeloid leukemia cases in pediatric and adult patients. Aberrant MLL signals were found in 18 patients: 11 (61.1%) with 3' MLL signal loss and 7 with 3' MLL signal gain. All cases with 3' MLL signal gain were due to an extra derivative partner chromosome. The median overall survival period of patients with 3' MLL gain was shorter than that in patients without aberrant MLL signal patterns. CONCLUSION: Aberrant MLL signals were frequently detected by FISH analysis. The 3' MLL gain was associated with poor prognosis in patients with AL. Therefore, it is important to detect aberrant MLL signal patterns using FISH analysis.
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