Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5. 1996

H Poirel, and K Rack, and E Delabesse, and I Radford-Weiss, and X Troussard, and C Debert, and D Leboeuf, and C Bastard, and F Picard, and A Veil-Buzyn, and G Flandrin, and O Bernard, and E Macintyre
Department of Haematology, University Paris V, France.

To determine the incidence of MLL rearrangement in acute myeloid leukemia (AML) French-American-British (FAB) type M1 and to evaluate optimal screening strategies for the characterization of such abnormalities, we analyzed specimens from 41 patients with AML by Southern blotting with two MLL genomic probes and compared the capacities of reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH) to identify the types of rearrangement found in AML M1 with those observed in AML M5. MLL rearrangement was found in 6 of 29 (20%) AML M1 and 6 of 10 AML M5 cases. RT-PCR characterization of 11 cases showed four MLL self-fusions, four MLL-AF6, two MLL-AF9, including a novel AF9 breakpoint, and one uncharacterized t(11:19). Only 5 of 10 MLL-rearranged cases tested demonstrated karyotypic 11q23 abnormalities. FISH analysis of nine cases with an MLL-specific yeast artificial chromosome (YAC) confirmed the cytogenetic abnormalities in two cases, clarified them in one, and did not detect six cases, including three MLL self-fusions, one case with a probable MLL-rearranged subclone not represented karyotypically, and twoMLL-AF6. A whole chromosome 11 paint detected one of these MLL-AF6, and an AF6 cosmid demonstrated that the other was probably due to insertion of a submicroscopic portion of chromosome 6, including part of AF6, into an apparently normal chromosome 11. We conclude that MLL rearrangements are common in adult AML M1, that MLL self-fusion and MLL-AF6 are the most frequent types of abnormalities, and that RT-PCR is preferable to 11q23 FISH analysis for their characterization.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007948 Leukemia, Monocytic, Acute An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES. Leukemia, Monoblastic, Acute,Leukemia, Myeloid, Acute, M5,Leukemia, Myeloid, Schilling-Type,Monoblastic Leukemia, Acute,Monocytic Leukemia, Acute,Myeloid Leukemia, Acute, M5,Myeloid Leukemia, Schilling-Type,Leukemia, Acute Monocytic,Leukemia, Myeloid, Schilling Type,Acute Monoblastic Leukemia,Acute Monoblastic Leukemias,Acute Monocytic Leukemia,Acute Monocytic Leukemias,Leukemia, Schilling-Type Myeloid,Leukemias, Acute Monoblastic,Leukemias, Acute Monocytic,Monoblastic Leukemias, Acute,Monocytic Leukemias, Acute,Myeloid Leukemia, Schilling Type,Schilling-Type Myeloid Leukemia
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D011495 Histone-Lysine N-Methyltransferase An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. Protein Lysine Methyltransferase,Protein Methylase III,Protein Methyltransferase III,Histone-Lysine Methyltransferase,Histone Lysine Methyltransferase,Histone Lysine N Methyltransferase,Methyltransferase, Histone-Lysine,Methyltransferase, Protein Lysine,N-Methyltransferase, Histone-Lysine
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children

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