MLL rearrangements in haematological malignancies: lessons from clinical and biological studies

DiMartino, Jorge; Cleary, Michael L.

doi:10.1046/j.1365-2141.1999.01439.x

Cited by 229 publications

(186 citation statements)

References 93 publications

(128 reference statements)

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“…A sequence homology search revealed that the D40 sequence is the same as that of the AF15q14 gene (Hayette et al, 2000). This gene is a partner that fuses with MLL, an oncogenic gene involved in the development of acute leukaemia (Hunger et al, 1993;Thirman et al, 1994;Hernandez et al, 1995;Dimartino and Cleary, 1999). In contrast to normal tissues, D40 was expressed in all human cancer cell lines examined and in several primary human tumours independently of the types and source of the tumours.…”

Section: Discussionmentioning

confidence: 99%

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

et al. 2002

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We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.

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Section: Discussionmentioning

confidence: 99%

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

et al. 2002

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“…3 The vast number of MLL partner genes that have been cloned to date share little sequence homology and associate preferentially to different subtypes of acute myeloblastic leukemia (AML), ALL (acute lymphoblastic leukemia), or myelodysplastic syndromes (MDS). 4 The MLL gene encodes for a predicted 431 kDa protein that is proteolytically processed into amino terminal p300 and carboxyl terminal p180 fragments, which form an MLL stable complex in vivo. [5][6][7] The resulting chimeric proteins include the amino terminal half of MLL fused in frame to different partner gene products where this heterogeneity of partner sequences, together with the impaired ability to complex with the carboxyl terminal p180 fragment highly homologous to trithorax, argue for a leukemogenic role played by the amino terminal half of MLL.…”

Section: Introductionmentioning

confidence: 99%

Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein

et al. 2004

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Acute lymphoblastic leukemia (ALLs) expressing MLL-AF4, the fusion product of t(4;11)(q21;q23), show marked leucocytosis and extramedullary disease in multiple organs, respond poorly to chemotherapy and have poor prognosis. In vitro, leukemic cells with the t(4;11) show resistance to serum deprivationinduced or interferon c-regulated CD95-mediated apoptosis. In addition, t(4;11) cells have prolonged doubling time and lower percentage of cells in cycle compared to non-t(4;11) B lineage cell lines. In this study, we examine the time-and leveldependent effects of MLL-AF4 conditional expression on cell cycle and differentiation of myelomonocytic leukemia cell line U937. By varying the concentration of tetracycline in growth media, we found that increasing levels of MLL-AF4 expression result in a progressive decrease in growth rate and fraction of S phase cells, paralleled by an increase in percentage of cells expressing CD11b. Our results demonstrate a dosage-dependent effect of MLL-AF4 fusion oncoprotein on cell cycle progression, with increasing expression levels resulting in the accumulation in G1, prolonged doubling time, both findings that might be responsible for the increased resistance to etoposide-mediated cytotoxicity. We propose the cell cycle control exerted by MLL-AF4 may be responsible of resistance to cell-death promoting stimuli in leukemia carrying the t(4;11) translocation.

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“…[1][2][3][4][5][6][7] Such translocations result in the expression of chimeric transcripts that are fused in frame between the MLL gene and various partner genes. The MLL gene encodes a 431-kDa protein, which comprises 3,969 amino acids.…”

Section: Introductionmentioning

confidence: 99%

Targeted down-regulation of MLL-AF9 with antisense oligodeoxyribonucleotide reduces the expression of the HOXA7and -A10 genes and induces apoptosis in a human leukemia cell line, THP-1

Kawagoe

Sano

2001

Leukemia

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MLL rearrangements in haematological malignancies: lessons from clinical and biological studies

Cited by 229 publications

References 93 publications

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein

Targeted down-regulation of MLL-AF9 with antisense oligodeoxyribonucleotide reduces the expression of the HOXA7and -A10 genes and induces apoptosis in a human leukemia cell line, THP-1

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