A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4

Kawamata, Norihiko; Sakajiri, Sakura; Sugimoto, Keiji; Isobe, Yasushi; Kobayashi, Hirofumi; Oshimi, Kazuo

doi:10.1038/sj.onc.1205628

Cited by 40 publications

(28 citation statements)

References 36 publications

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“…Through yeast two-hybrid screening, using the synovial sarcoma-associated SSX1 C terminus as a bait, we isolated two cDNAs corresponding to the LHX4 protein, a transcription factor that is known to be involved in pituitary and motor neuron development (Sheng et al, 1997;Sharma et al, 1998;Machinis et al, 2001;Raetzman et al, 2002) and to be deregulated and/ or translocated in human chronic myeloid and acute lymphoblastic leukemias (Wu et al, 1996;Dong et al, 1997;Wu and Minden, 1997;Kawamata et al, 2002;Yamaguchi et al, 2003). In the yeast two-hybrid system, the LHX4 protein interacts equally well with the C terminus of all SSX proteins known to be involved in synovial sarcoma, that is SSX1, SSX2 and SSX4.…”

Section: Discussionmentioning

confidence: 99%

“…Ectopic expression of the LHX1 and LHX2 genes has, for example, been detected in various leukemias (Wu et al, 1996;Dong et al, 1997;Wu and Minden, 1997) and stable expression of the LHX2 gene in hematopoietic stem cells, engrafted in stem cell-deficient mice, has been shown to cause myeloproliferative disorders and acute leukemias (Richter et al, 2003). In cellular transformation assays, using Rat1 and NIH3T3 cell lines, the oncogenic activities of the LHX4 gene could not be defined (Kawamata et al, 2002), but aberrant expression of this gene was observed in the case of chronic myeloid leukemia in blast crisis and in the case of pre-B acute lymphoblastic leukemia. Both cases carried a t(1;14)(q25;q32) chromosome translocation, which The SSX C terminus interacts with LHX4 DRH de Bruijn et al resulted in juxtaposition of the respective LHX4 and IGH genes (Kawamata et al, 2002;Yamaguchi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In cellular transformation assays, using Rat1 and NIH3T3 cell lines, the oncogenic activities of the LHX4 gene could not be defined (Kawamata et al, 2002), but aberrant expression of this gene was observed in the case of chronic myeloid leukemia in blast crisis and in the case of pre-B acute lymphoblastic leukemia. Both cases carried a t(1;14)(q25;q32) chromosome translocation, which The SSX C terminus interacts with LHX4 DRH de Bruijn et al resulted in juxtaposition of the respective LHX4 and IGH genes (Kawamata et al, 2002;Yamaguchi et al, 2003). The LHX4 gene was also found to be overexpressed in the pre-B acute lymphoblastic leukemia cell line MD930 (Yamaguchi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The LHX4 gene was also found to be overexpressed in the pre-B acute lymphoblastic leukemia cell line MD930 (Yamaguchi et al, 2003). During normal development, the LHX4 gene is predominantly expressed in the central nervous system (Liu et al, 2002), and it was proposed that its overexpression may be associated with cellular proliferation and/or anti-apoptosis (Kawamata et al, 2002;Yamaguchi et al, 2003). Indeed, mouse knockout studies revealed that LHX4 deficiency leads to an increased apoptotic rate in Rathke's pouch, resulting in an impaired pituitary development reminiscent of human congenital pituitary hormone deficiency (CPHD; Sheng et al, 1997;Machinis et al, 2001;Raetzman et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Our The SSX C terminus interacts with LHX4 DRH de Bruijn et al data indicate that the C terminus of the SSX1, SSX2 and SSX4 proteins interact in vivo with the LIM homeobox protein LHX4. This transcription factor was previously found to be deregulated and/or translocated in chronic and acute leukemias (Wu et al, 1996;Dong et al, 1997;Wu and Minden, 1997;Kawamata et al, 2002;Yamaguchi et al, 2003). The putative implications of these novel protein -protein interactions for the development of human synovial sarcomas and other SSX-positive tumors are discussed.…”

Section: Introductionmentioning

confidence: 87%

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The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4

et al. 2007

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As a result of the synovial sarcoma-associated t(X;18) translocation, the SS18 gene on chromosome 18 is fused to either one of the three closely related SSX genes on the X chromosome. The SS18 protein is thought to act as a transcriptional co-activator, whereas the SSX proteins are thought to act as transcriptional corepressors. The main SSX-repression domain is located in its C terminus, a domain that is retained in the respective SS18-SSX fusion proteins. Both the SS18 and SSX proteins lack DNAbinding domains. Previously, we found that the SS18 and SS18-SSX fusion proteins may be tethered to DNA targets via the SS18-interacting protein AF10. Here, we set out to isolate proteins that interact with the SSX C-terminal repression domain using a yeast two-hybrid interaction trap. Of the positive clones isolated, two corresponded to the LIM homeobox protein LHX4, a DNA-binding protein that is involved in transcription regulation. An endogenous interaction was subsequently established in mammalian cells via colocalization and coimmunoprecipitation of the respective proteins. Interestingly, the LHX4 gene was previously found to be deregulated in various human leukemias. In addition, it was previously found that LIM homeobox proteins may bind to and activate the glycoprotein-a (CGA) promoter. Using LHX4 chromatin immunoprecipitation and CGApromoter assays, we found that endogenous LHX4 binds to the CGA promoter and that LHX4-mediated CGA activation is enhanced by the SS18-SSX protein, but not by the SSX protein. Taken together, we conclude that this novel protein -protein interaction may have direct consequences for the (de)regulation of SSX and/or SS18-SSX target genes and, thus, for the development of human synovial sarcomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

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The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4

et al. 2007

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Aberrant expression of the LHX4 LIM‐homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis

Yamaguchi

Yamamoto

Miura

2003

Genes Chromosomes & Cancer

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Chromosomal aberrations observed in addition to the Philadelphia chromosome in chronic myelogenous leukemia (CML) are likely to be involved in disease progression to the blast crisis. We describe here a t(1;14)(q25;q32) as an additional chromosomal aberration in a patient with CML in biphenotypic blast crisis. By use of long-distance inverse polymerase chain reaction (PCR), we cloned the chromosomal breakpoint and revealed that the immunoglobulin heavy chain gene is fused near its Emu enhancer region to the 5' region of the LHX4 LIM-homeobox gene, whose expression is restricted to the central nervous system. By use of quantitative real-time reverse-transcription PCR, we found that the LHX4 mRNA is expressed at high levels in the patient's leukemic cells and in an acute lymphoblastic leukemia (ALL) cell line. The aberrant expression of the LHX4 gene by the t(1;14)(q25;q32) has very recently been reported in a case of ALL, thus, representing a rare, but recurrent genetic abnormality of possible importance in leukemogenesis.

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t(14;19)(q32;q13): A recurrent translocation in B‐cell precursor acute lymphoblastic leukemia

Robinson

Taylor

Jalali

et al. 2003

Genes Chromosomes & Cancer

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The recurrent t(14;19)(q32;q13) translocation associated with chronic B-cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B-cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus-specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)-positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B-cell precursor acute lymphoblastic leukemia.

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A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4

Cited by 40 publications

References 36 publications

The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4

The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4

Aberrant expression of the LHX4 LIM‐homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis

t(14;19)(q32;q13): A recurrent translocation in B‐cell precursor acute lymphoblastic leukemia

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