A study on 289 consecutive Korean patients with acute leukaemias revealed fluorescence in situ hybridization detects the MLL translocation without cytogenetic evidence both initially and during follow‐up

Abstract

Summary. Translocations involving the MLL gene on the chromosome 11 (11q23) are frequently observed in acute leukaemia. The detection of this genetic change has a unique significance as a result of its implication of poor prognosis. To reveal the utility of fluorescence in situ hybridization (FISH) in detecting the MLL translocation, we analysed 289 consecutive Korean patients (children and adults) with acute leukaemias using both conventional cytogenetic analysis (CC) and FISH, placing an emphasis on the result discrepancies. Twenty-two of 289 patients (7AE6%) had the 11q23/MLL translocation. In nine of 22 patients (41%), only FISH detected the translocation. In eight of these 22 patients, a total of 19 follow-up examinations were performed, of which FISH detected a significant level of leukaemic cells harbouring the MLL translocation in five patients (26%) without cytogenetic evidence. In addition to the MLL translocation, FISH detected submicroscopic amplification, partial deletion of the MLL gene and trisomy 11 in 12 patients without cytogenetic evidence. In summary, up to 41% of the MLL translocations at initial work-up and 26% during follow-up were detected by FISH without cytogenetic evidence. Thus, we recommend that MLL FISH should be performed in the diagnosis and monitoring of acute leukaemias in combination with CC.Keywords: acute leukaemia, 11q23 translocation, MLL, cytogenetic analysis, fluorescence in situ hybridization.Human leukaemia is now recognized as an acquired genetic disease. A large number of consistent chromosomal changes have been identified and some of these have provided unique insights into the understanding of the pathogenesis of the disease (Heim & Mitelman, 1995;Look, 1997). Karyotypic analysis to identify chromosomal abnormalities is now part of the routine work-up for diagnostic and riskstratification studies for determining the appropriate therapy in newly diagnosed and relapsed leukaemia patients. Structural abnormalities involving the q23 band of chromosome 11 (11q23) are probably the most common of the many identified genetic abnormalities in haematological malignancies, and the majority of these involve the MLL (myeloid/lymphoid leukaemia or mixed lineage leukaemia) gene, which is also known as ALL-1, HRX and HTRX1 (Thirman et al, 1993). The MLL gene is located on 11q23 and contains more than 30 exons. Translocation involving this gene usually occurs between exons 5 and 11, which is known as the breakpoint cluster region (Djabali et al, 1992;Gu et al, 1992). The translocation of this gene occurs in approximately 5-8% of acute myeloid leukaemias (AML), 7-10% of acute lymphoblastic leukaemias (ALL) and in 60-70% of infant leukaemias, irrespective of the phenotype (Thirman et al, 1993;Pui et al, 1995). The 11q23/MLL translocation is known to be associated with acute leukaemia in infancy and with therapy-related leukaemia, and this translocation in acute leukaemia implies a poor prognosis although there is some disagreement on this issue (Cimino et al, 1995;Rubnitz et al, 1997)...

ABL oncogene amplification with p16INK4a gene deletion in precursor T‐cell acute lymphoblastic leukemia/lymphoma: Report of the first case

“…The centromeric signals serve as internal control to rule out increased number of gene signals due to polysomy. The expanding application of molecular cytogenetic technique has rendered amplification of such genes as MYC, MLL, and AML1 more readily detectable [12][13][14][15]. The cases hitherto reported on gene amplification in hematologic malignancies mostly involved acute myeloid leukemia (AML), and CMYC appears to be the most frequently amplified gene in AML.…”

First description of the t(10;11)(q22;q23)/MLL-TET1 translocation in a T-cell lymphoblastic lymphoma, with subsequent lineage switch to acute myelomonocytic myeloid leukemia

“…1 So far, 13 cases have been reported in the literature, 11 in acute myeloid leukemia (AML) patients [1][2][3][4][5][6][7][8] and 2 in B-cell precursor acute lymphoblastic leukemia (ALL). 9 It was also recently reported that MLL is fused to TET1 in only 5 out of 1,590 MLL rearranged AML cases (0.3%).…”

“…As proposed by Lee et al, we confirm the need to collect and report more cases and to test the leukemogenic activity of MLL-TET1 associated to demethylating agents in a murine bone marrow transduction/transplantation model system. Antoine Ittel, 1,2,3 Eric Jeandidier, 3,4 Catherine Helias, 1,3 Nathalie Perrusson, 2 Catherine Humbrecht, 4 Bruno Lioure, 5 Isabelle Mazurier, 6 Caroline Mayeur-Rousse, 1 Amandine Lavaux, 3,4 Sylvie Thiebault, 8 Felix Lerintiu, 9 Carine Gervais, 1,3 …”

Genomic breakpoints and clinical features of MLL-TET1 rearrangement in acute leukemias

“…[4][5][6][7][8][9][10][11] There has been little research into the common features of MLL-TET1 rearrangements. Here we provide information about molecular and clinical characterization of MLL-TET1 rearrangements diagnosed in 3 AML patients.…”

“…We summarized the published data to evaluate patients' characteristics (Table 2). [4][5][6][7][8][9][10][11] A molecular characterization at the genomic or transcript level was performed only for a subset of patients. Eight of 11 AML patients (72.7%) were classified as FAB-M4/M5 subtypes; 7 men and 5 women with a median age of 38.0 years (range 1 month to 67 years).…”