HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell leukemia patient

Fujimoto, Rika; Ozawa, Tatsuhiko; Itoyama, Takahiro; Sadamori, Naoki; Kurosawa, Nobuyuki; Isobe, Masaharu

doi:10.1016/j.cancergen.2012.04.006

Cited by 15 publications

(17 citation statements)

References 28 publications

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“…Thus, the fusion, which contains only exons 1 to 2 of IKZF2, co-opts the IKZF2 promoter for expression. 46 These findings complement a recent report of truncated ERBB4 transcripts promoted by intronic long terminal repeats in ALCL, which retain ERBB4 kinase activity and are sensitive to ERBB family kinase inhibitors such as lapatinib. 47 Examination of exon-level read plots for genes involved in the remaining fusions in Table 1 demonstrated 2 additional events with altered read counts in the case of interest: diminished CD58 expression in TCL81 (COPA-CD58 fusion; supplemental Figure 3A) and increased ZNF541 expression (exons 11-15) in TCL66 (GSK3A-ZNF541 fusion; supplemental Figure 3B).…”

Section: Mpseq/rnaseq Identifies Novel Kinase Fusions In Ptcl Nossupporting

confidence: 77%

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Boddicker¹,

Razidlo

Dasari

et al. 2016

Blood

103

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Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of T-cell malignancies that generally demonstrate aggressive clinical behavior, often are refractory to standard therapy, and remain significantly understudied. The most common World Health Organization subtype is PTCL, not otherwise specified (NOS), essentially a “wastebasket” category because of inadequate understanding to assign cases to a more specific diagnostic entity. Identification of novel fusion genes has contributed significantly to improving the classification, biologic understanding, and therapeutic targeting of PTCLs. Here, we integrated mate-pair DNA and RNA next-generation sequencing to identify chromosomal rearrangements encoding expressed fusion transcripts in PTCL, NOS. Two of 11 cases had novel fusions involving VAV1, encoding a truncated form of the VAV1 guanine nucleotide exchange factor important in T-cell receptor signaling. Fluorescence in situ hybridization studies identified VAV1 rearrangements in 10 of 148 PTCLs (7%). These were observed exclusively in PTCL, NOS (11%) and anaplastic large cell lymphoma (11%). In vitro, ectopic expression of a VAV1 fusion promoted cell growth and migration in a RAC1-dependent manner. This growth was inhibited by azathioprine, a clinically available RAC1 inhibitor. We also identified novel kinase gene fusions, ITK-FER and IKZF2-ERBB4, as candidate therapeutic targets that show similarities to known recurrent oncogenic ITK-SYK fusions and ERBB4 transcript variants in PTCLs, respectively. Additional novel and potentially clinically relevant fusions also were discovered. Together, these findings identify VAV1 fusions as recurrent and targetable events in PTCLs and highlight the potential for clinical sequencing to guide individualized therapy approaches for this group of aggressive malignancies.

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Section: Mpseq/rnaseq Identifies Novel Kinase Fusions In Ptcl Nossupporting

confidence: 77%

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Boddicker¹,

Razidlo

Dasari

et al. 2016

Blood

103

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“…BCL11B overexpression has been reported in an acute type of ATLL regardless of the gain/amplification of 14q32 [26]. We recently reported the expression of a BCL11B-HELIOS fusion gene in an ATLL patient with t(2;14)(q34;q32) [27]. These reports underscore the potential importance of BCL11B in T-cell maturation and in the development of T-cell malignancies.…”

Section: Introductionmentioning

confidence: 61%

“…Southern blotting and adaptor ligated-PCR were conducted as previously described [27]. The amplification products were cloned into the pBlueScript SK(−) plasmid vector.…”

Section: Methodsmentioning

confidence: 99%

Reduced Level of the BCL11B Protein Is Associated with Adult T-Cell Leukemia/Lymphoma

et al. 2013

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BackgroundAdult T-cell leukemia/lymphoma (ATLL) develops in a small proportion of human T-cell leukemia virus type I (HTLV-I)-infected individuals. However, the mechanism by which HTLV-I causes ATLL has not been fully elucidated. To provide fundamental insights into the multistep process of leukemogenesis, we have mapped the chromosomal abnormalities in 50 ATLL cases to identify potential key regulators of ATLL.ResultsThe analysis of breakpoints in one ATLL case with the translocations t(14;17)(q32;q22-23) resulted in the identification of a Kruppel zinc finger gene, BCL11B, which plays a crucial role in T-cell development. Among the 7 ATLL cases that we examined by immunofluorescence analysis, 4 displayed low and one displayed moderate BCL11B signal intensities. A dramatically reduced level of the BCL11B protein was also found in HTLV-I-positive T-cell lines. The ectopic expression of BCL11B resulted in significant growth suppression in ATLL-derived cell lines but not in Jurkat cells.ConclusionsOur genetic and functional data provide the first evidence that a reduction in the level of the BCL11B protein is a key event in the multistep progression of ATLL leukemogenesis.

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“…jci.org Volume 125 Number 3 March 2015 found in T cell ALL suggesting a dominant-negative function (57). HOXA9 is considered to be one of the most critical downstream targets of MLL-related oncogenes.…”

Section: 9mentioning

confidence: 99%

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

Park¹,

Gönen²,

Vu³

et al. 2015

J. Clin. Invest.

116

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HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell leukemia patient

Cited by 15 publications

References 28 publications

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Reduced Level of the BCL11B Protein Is Associated with Adult T-Cell Leukemia/Lymphoma

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

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