MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Group (UKCCG) study

Abstract

The MLL gene, located at 11q23, is frequently rearranged in acute leukaemia as either chimaeric fusion genes or partial tandem duplications. We report a series of 12 acute leukaemia cases with apparent amplification of the MLL gene ascertained using fluorescence in situ hybridisation (FISH). Seven cases showed intrachromosomal amplification of MLL, four cases showed extrachromosomal amplification as double minute chromosomes (dmin) and one case had separate subclones with dmin and homogenously staining region (hsr). Southern blot analysis of the MLL gene showed MLL gene rearrangement in three of the 10 successful cases. These cases do not naturally fall into either of the two recognised categories of MLL rearrangement and may represent a third variety of MLL gene abnormalities.

Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia

“…Cytogenetically, amplifications are frequently associated with double minutes or homogenously staining regions. 21,22 which were never observed in our series. We found cryptic 6p gains at the translocation breakpoints of der(6) in cases with duplications and/or within derivative chromosome partners in cases with low-copy gains.…”

Amplification of the ABL gene in T-cell acute lymphoblastic leukemia

“…Amplifications of the MYC and MLL genes have been previously reported in acute myeloid leukemia (AML), [2][3][4] and of AML1 and MLL in ALL. 3,5 Although amplification of the BCR/ABL fusion gene has been described in cases of chronic myeloid leukemia (CML) treated with imatinib mesylate, seen both as HSRs 6 and dmins, 7 amplification of ABL alone is rare. A six-fold and a 15-fold amplification of the gene have been described in the CML-derived cell line, K562, 8 and in a patient with CML in lymphoid blast crisis, respectively.…”

“…2 Interferon use immediately post-allogeneic transplant may reduce the relapse rate through stimulation of an immunologic response. 3 Finally, multiple studies show statistically significant reductions in relapse rates in patients who develop acute GVHD, chronic GVHD or both. 4 Unfortunately, the efficacy of a GVL effect in the context of DLI for ALL relapse post-transplant is quite unimpressive.…”

Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies

“…In cases with 11q23 amplification, the MLL gene was consistently shown to be amplified, 2,5,7,[10][11][12][13][14] although double minute chromosomes containing more distally located sequences have been described occasionally. 15,16 Using fluorescence in situ hybridization (FISH) with MLL flanking probes, 2 distinct patterns were identified: MLL amplification on homogeneously staining regions or double minutes and MLL low-copy gain due to the retention of MLL copies on extra or derivative chromosomes 11.…”