Identification of Amplified Genes in a Patient with Acute Myeloid Leukemia and Double Minute Chromosomes

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

“…[22][23][24] Of these, 10 were shown to contain MYC sequences (normally located at 8q24), three showed amplification of MLL sequences 10,12 and one showed amplification of various genes on 11q23-24. 22 Our study contributes a further five acute leukaemias with MLL sequences present on dmin. Case 12 demonstrates one abnormal clone with MLL positive dmin whilst another clone shows no dmin, but a MLL positive hsr.…”

BLIMP1α, the master regulator of plasma cell differentiation is a tumor supressor gene in B cell lymphomas

“…Deleterious mutations of PRDM1 associated with loss of BLIMP1 protein have also been reported in primary central nervous system lymphoma 63 . Finally, ETS-1, the transcription factor, which is amplified in certain leukemias, interacts with BLIMP1 leading to a block in BLIMP1 DNA binding activity and a reduction in the ability of BLIMP1 to repress target genes [64][65][66][67][68] . In contrast, the over-expression of the BLIMP1β isoform has been reported in multiple myeloma, DLBCL and in some T cell lymphomas 6,[69][70][71] .…”

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

“…Karyotypic analysis was performed on G-, R-or Q-banded metaphases in all cases; karyotypes of patients no. 1 to 6, 8 to 10,14,15,17,18,20,21,24, and 28 to 30 were further characterized using spectral karyotyping or multiplex FISH (Table 1). The karyotypes were described according to the 1995 recommendations of the International System for Human Cytogenetic Nomenclature (ISCN).…”

“…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. In view of the consistent overrepresentation of MLL in the reported leukemias with 11q23 gain or amplification and given the putative gain of function of the gene as a result of fusion with various partner genes, this oncogene was assumed to be a prime target that drives the 11q23 amplicon formation.…”