Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23)

Hiwatari, Mitsuteru; Taki, Tomohiko; Taketani, Takeshi; Taniwaki, Masafumi; Sugita, Kenichi; Okuya, Mayuko; Eguchi, Mitsuoki; Ida, Kohmei; Hayashi, Yasuhide

doi:10.1038/sj.onc.1206389

Cited by 40 publications

(42 citation statements)

References 21 publications

(28 reference statements)

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“…The conditions and reagents for PCR have been already described (Ono et al, 2002a, b;Hiwatari et al, 2003). The primers used were as follows: ALL-7S and SS-2A, 5 0 -AATGGCGTCTTCGGT GATCTG-3 0 .…”

Section: Rt-pcr and Genomic Pcrmentioning

confidence: 99%

“…Aliquots (10 mg) of total RNA derived from each cell line and multiple human tissue Northern blots (CLONTECH Laboratories, Inc., CA, USA) were analysed with a 32 P-labeled MYO1F cDNA probe (Ono et al, 2002a, b;Hiwatari et al, 2003). A 174-bp MYO1F cDNA fragment (nucleotides 39-213 from sequences of MYO1F cDNA, GenBank Accession number BC028071) was used.…”

Section: Northern Blot Analysismentioning

confidence: 99%

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The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22

et al. 2005

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Section: Rt-pcr and Genomic Pcrmentioning

confidence: 99%

Section: Northern Blot Analysismentioning

confidence: 99%

The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22

et al. 2005

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“…After the juxtaposition of SOX5 coding sequence to the P2RY8 (G-protein coupled purinergic receptor P2Y8) promoter sequence, A novel fusion 5 0 AFF3/3 0 BCL2 in follicular lymphoma L Impera et al it was highly active in lymph nodes and in lymph (Storlazzi et al, 2007). The AFF3 promoter is reported to be highly expressed in lymphoid tissues (Hiwatari et al, 2003). Rearrangements of the BCL2 gene are recurrent in B-cell tumors.…”

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confidence: 99%

“…The partner AFF3 gene encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential and is thought to have a role in early lymphoid development (Hiwatari et al, 2003). The AFF3 is a member of a family of proteins including AFF1 (4q21.3-22.1, also known as AF4), AFF2 (Xq28, alias FMR2) and AFF4 (5q31.1, alias AF5q31), which have various similarities: size of transcripts, protein size of approximately 1300 amino acids and nuclear localization of the proteins.…”

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confidence: 99%

“…Similarly, AFF3 has been implicated in tumorigenesis, as it was reported to be the 3 0 fusion partner of MLL (5) and RUNX1 (Chinen et al, 2008) in pediatric ALL, respectively, with B-ALL and T-ALL phenotype. In both chimeras, the breakpoint disrupting AFF3 was located within the region homologous to the transactivation domain of AFF1 and AFF4 (exons 5-7), leading to the retention of this oncogenic domain in all the AFF3 fusion proteins (Hiwatari et al, 2003;Chinen et al, 2008). In this case, the AFF3 breakpoint was located within the 5 0 UTR region, that is, outside its coding region.…”

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A novel fusion 5′AFF3/3′BCL2 originated from a t(2;18)(q11.2;q21.33) translocation in follicular lymphoma

et al. 2008

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Follicular lymphoma is the second most frequent type of non-Hodgkin's lymphoma in adults. The basic molecular defect consists of the t(14;18)(q32;q21) translocation, juxtaposing the B-cell lymphoma protein 2 gene BCL2 to the immunoglobulin heavy chain locus IGH@, and leading to the antiapoptotic BCL2 protein overproduction. Variations in the t(14;18) are rare and can be classified into two categories: (i) simple variants, involving chromosomes 18 and 2, or 22, in which the fusion partner of BCL2 is the light-chain IGK@ or IGL@; (ii) complex variant translocations occurring among chromosomes 14, 18 and other chromosomes. We report a follicular lymphoma case showing BCL2 overexpression, detected by immunohistochemistry and real-time quantitative PCR, consequently to the formation of a novel fusion gene between the 5 0 of the lymphoid nuclear transcriptional activator gene AFF3 at 2q11.2, and the 3 0 of BCL2. This case shows evidence, for the first time, of BCL2 overexpression consequently to the fusion of BCL2 to a non-IG partner locus.Oncogene ( Keywords: AFF3; BCL2; fusion gene; follicular lymphoma; translocation Follicular lymphoma (FL) is the second most frequent type of non-Hodgkin's lymphoma in adults (de Jong, 2005). The t(14;18)(q32;q21) translocation juxtaposes the B-cell lymphoma protein 2 gene (BCL2), at 18q21, to the immunoglobulin heavy chain locus (IGH@) at 14q32. This rearrangement leads to the overproduction of the antiapoptotic BCL2 protein, the basic molecular defect in FL.Variations in the t(14;18) are rare and can be classified into two categories: (i) simple variants, involving chromosome 18 and either chromosome 2 or 22, in which the fusion partner of BCL2 is the light-chain IGK@ (2p11.2) or IGL@ (22q11.2); (ii) complex variant translocations, involving chromosomes 14, 18 and one or two other chromosomes (Bentley et al., 2005). Such variants can be considered as biologic equivalents of the t(14;18) and, therefore, more than 90% of indolent FLs express high levels of BCL2 protein (de Jong, 2005).Here we describe a FL case showing BCL2 overexpression, detected by immunohistochemistry and realtime quantitative PCR. This case is the result of the fusion of the 3 0 end of BCL2 with the 5 0 of AFF3 (AF4/ FMR2 family member 3 isoform 1, also known as LAF4) at 2q11.2. The chimeric gene was investigated by RT-PCR and fluorescent in situ hybridization analyses.A 65-year-old female patient was referred to our hospital because of persistent submandibular and multiple cervical lymphadenopathy. The patient did not complain of fatigue, night sweats or significant weight loss. Laboratory findings showed elevated lactate dehydrogenase and hypergammaglobulinemia. Other biochemical values were in the normal range. A total body computerized axial tomographic scan showed enlargement of multiple submandibular, cervical, axillary and mediastinal lymph nodes. Submandibular lymph node biopsy was performed. Immunophenotyping showed positivity for CD10 and CD20. No evidence of lymphoma involvement was found in the bone...

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LAF‐4 is aberrantly expressed in human breast cancer

Faseruk

Gökgöz

et al. 2005

Intl Journal of Cancer

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LAF‐4, which encodes a nuclear protein with transactivation potential, is fused to the MLL gene in acute lymphoblastic leukemia (ALL). We identified LAF‐4 as a gene that is transcriptionally deregulated in breast tumors and thus may have a pathological role in mammary tumorigenesis. In line with the previous finding that LAF‐4 expression is tissue specific, we did not detect any LAF‐4 mRNA in normal mammary epithelial cell lines. However, 2 of 5 breast cancer cell lines were found to express LAF‐4 at both the RNA and protein levels. In 2 of 9 primary tumor‐normal pairs, the expression of LAF‐4 was clearly elevated in the tumor tissue. Using RNA in situ hybridization, we demonstrated that LAF‐4 is expressed in mammary tumor cells but not in normal acini. In a group of 64 primary human breast tumors, we found that LAF‐4 was overexpressed in approximately 20% of the cases. Although epigenetic changes may be involved in altered expression of some genes, differences in LAF‐4 expression were not associated with DNA methylation of the predicted promoter region. Our results suggest that LAF‐4 may be a proto‐oncogene that is transcriptionally activated in some cases of breast cancer. © 2005 Wiley‐Liss, Inc.

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Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23)

Cited by 40 publications

References 21 publications

The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22

The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22

A novel fusion 5′AFF3/3′BCL2 originated from a t(2;18)(q11.2;q21.33) translocation in follicular lymphoma

LAF‐4 is aberrantly expressed in human breast cancer

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