Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias.

Poel, S Ziemin-van der; McCabe, Norah R.; Gill, Heidi; Espinosa, Rafael; Patel, Yogesh; Harden, Alanna M.; Rubinelli, P; Smith, Stephen D.; LeBeau, Michelle M.; Rowley, Janet D.

doi:10.1073/pnas.88.23.10735

Cited by 546 publications

(305 citation statements)

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“…7,8 As these aberrations were found in AML as well as acute lymphoblastic leukemia (ALL), the gene was called mixedlineage leukemia. 9 Recent studies show that the MLL group itself is genetically and clinically heterogeneous, as more than 60 different translocation partners of the MLL gene with differences in outcome have been described to date. 6,10 The biological background of these differences remains unknown.…”

Section: Introductionmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

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Section: Introductionmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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“…The analysis of chromosomal translocations a ecting chromosome 11 at band q23 in leukaemias has shown that these events involve fusions between the human trithorax (MLL) gene (Djabali et al, 1992;Gu et al, 1992;Tkachuk et al, 1992;Ziemin-van der Poel et al, 1991) and a variety of partner genes each providing a COOH region to the resultant fusion protein. These translocations result in in-frame fusions suggesting an important role for the di erent COOH regions in the oncogenic transformation.…”

Section: Introductionmentioning

confidence: 99%

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

McCullagh¹,

Chaplin²,

Meerabux³

et al. 1999

Oncogene

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The MLL gene is reciprocally translocated with one of a number of di erent partner genes in a proportion of human acute leukaemias. The precise mechanism of oncogenic transformation is unclear since most of the partner genes encode unrelated proteins. However, two partner genes, AF10 and AF17 are related through the presence of a cysteine rich region and a leucine zipper. The identi®cation of other proteins with these structures will aid our understanding of their role in normal and leukaemic cells. We report the cloning of a novel human gene (BRL) which encodes a protein containing a cysteine rich region related to that of AF10 and AF17 and is overall most closely related to the previously known protein BR140. BRL maps to chromosome 22q13 and shows high levels of expression in testis and several cell lines. The deduced protein sequence also contains a bromodomain, four potential LXXLL motifs and four predicted nuclear localization signals. A monoclonal antibody raised to a BRL peptide sequence con®rmed its widespread expression as a 120 Kd protein and demonstrated localization to the nucleus within spermatocytes.

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“…The mixed lineage leukemia (MLL) gene was isolated as a common target of chromosomal translocations observed in human acute leukemias [Ziemin-van der Poel et al, 1991;Gu et al, 1992;Tkachuk et al, 1992;Thirman et al, 1993]. Cytogenetic analyses have identified more than 50 different loci which translocate to MLL, resulting in either acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) [Rowley, 1998].…”

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confidence: 99%

MLL: How complex does it get?

Popovic

Zeleznik‐Le

2005

J of Cellular Biochemistry

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The mixed lineage leukemia (MLL) gene encodes a very large nuclear protein homologous to Drosophila trithorax (trx). MLL is required for the proper maintenance of HOX gene expression during development and hematopoiesis. The exact regulatory mechanism of HOX gene expression by MLL is poorly understood, but it is believed that MLL functions at the level of chromatin organization. MLL was identified as a common target of chromosomal translocations associated with human acute leukemias. About 50 different MLL fusion partners have been isolated to date, and while similarities exist between groups of partners, there exists no unifying property shared by all the partners. MLL gene rearrangements are found in leukemias with both lymphoid and myeloid phenotypes and are often associated with infant and secondary leukemias. The immature phenotype of the leukemic blasts suggests an important role for MLL in the early stages of hematopoietic development. Mll homozygous mutant mice are embryonic lethal and exibit deficiencies in yolk sac hematopoiesis. Recently, two different MLL-containing protein complexes have been isolated. These and other gain-and loss-of-function experiments have provided insight into normal MLL function and altered functions of MLL fusion proteins. This article reviews the progress made toward understanding the function of the wild-type MLL protein. While many advances in understanding this multifaceted protein have been made since its discovery, many challenging questions remain to be answered. J. Cell. Biochem. 95: 234-242, 2005. ß 2005 Wiley-Liss, Inc.

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Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias.

Cited by 546 publications

References 18 publications

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

MLL: How complex does it get?

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