Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RhoH/TTF (ARHH) gene encodes a new member of the Ras superfamily of small GTPases. The gene was identified by fusion to the BCL6/LAZ3 oncogene in an initially described t(3;4)(q27;p11) translocation in a non-Hodgkin's lymphoma cell line. The predicted amino acid sequence of the RhoH/TTF gene product includes Rho-like GTPase structural motifs. The RhoH/TTF gene is restrictively expressed in hematopoietic cells and tissues. Mutations in the human RAS genes have been shown previously to be tumorigenic; in the search for a potential implication of the RhoH/TTF gene in hemopoietic malignancies, we established its genomic structure. The RhoH/TTF gene spans 35 kb and contains two exons, with the second bearing the entire amino-acid-coding region. Chromosomal mapping, by FISH experiments, places the RhoH/TTF gene on the short arm of chromosome 4, band p13.
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PMID:Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. 922 77

We recently isolated the RhoH/TTF gene by its fusion to the LAZ3/BCL6 gene, in a non-Hodgkin's lymphoma (NHL) cell line, which bore a t(3;4)(q27;p11-13) translocation. This gene encodes a novel Rho GTP-binding protein and is specifically expressed in hematopoietic tissues. We made its precise mapping at band 4p13, and described its partial genomic structure. Using fluorescence in situ hybridization and molecular analyses, we report here on the rearrangement of the RhoH/TTF gene, at band 4p13, in four cases of NHL with t(3;4)(q27;p13) translocation and its fusion to the LAZ3/BCL6 gene at band 3q27, in three of these cases. RT-PCR analysis of two cases allowed the detection of variable fusion transcripts emerging from the rearranged alleles, and in one case, a deregulated expression of both RhoH/TTF and LAZ3/BCL6 genes, by promoter substitution, was observed. We also show here another rearrangement of the RhoH/TTF gene in a patient with multiple myeloma and t(4;14)(p13;q32) translocation, with breakage within the IGH gene. It is the first report which describes the recurrent chromosomal alteration of a GTP-binding protein encoding gene, in patients with hematopoietic malignancies.
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PMID:Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. 1080 63

Evaluating the potential benefit of the new anthracycline, idarubicin (Ida), in lymphoma, 58 tumour samples from patients suffering from low-grade non-Hodgkin's lymphoma (L-NHL), were analysed in vitro for their sensitivity to 0.5 microg/ml Ida. This was compared with the sensitivity to other anthracyclines (0.5 microg/ml), using the fluorometric microculture cytotoxicity assay. A total of 132 samples from patients with acute leukaemia and a cell-line panel representing different resistance mechanisms was included for comparison. The median cell survival of L-NHL cells did not differ after exposing the cells to Ida or daunorubicin (Dnr), whereas epirubicin, doxorubicin (Dox) and mitoxantrone (Mitox) were significantly less cytotoxic than Ida (P < 0.001). The median cell survival in L-NHL cells did not differ from that of acute leukaemia cells after exposure to 0.5 microg/ml Ida, Dnr, Dox and Mitox. Cells from previously treated patients with L-NHL had a higher median survival than cells from untreated patients after exposure to all drugs, except for Ida. In samples from previously untreated patients, Spearman rank correlations were high (Rho = 0.81-0.90) between cell survival after exposure to Ida and the other anthracyclines. The same pattern was observed in the cell-line panel (Rho = 0.78-0.91) (P < 0.05). In contrast, low correlations (Rho = 0.24-0.42) were observed among samples from previously treated patients. Our results indicate a potential benefit of Ida in previously drug-treated patients with L-NHL.
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PMID:In vitro evaluation of the efficacy of idarubicin in human tumour cells from patients with low-grade non-Hodgkin's lymphoma. 1202 23

The hematopoiesis-specific RhoH gene is thought to be deregulated in B-cell non-Hodgkin's lymphoma (B-NHL), by either a chromosomal translocation or mutations, which affect its 5' regulatory region. The encoded Rho protein, always GTP-bound in vivo, was hypothesized to behave as a Rac antagonist. Extensive expression analysis allowed the detection of RhoH transcripts in all hematopoietic lineages (lymphoid, erythroid, myeloid), with a high level in lymphoid cells. To initiate investigations on the molecular mechanisms that regulate RhoH gene expression, Race-PCR and primer extension were conducted in the B-cell line Raji, which allowed (i) the establishment of RhoH complex intron/exon organization and (ii) the detection of several transcription initiation sites. In addition, a high 5' end heterogeneity of RhoH mRNAs was observed, due to alternative splicing of some 5' exons and to the use of these different transcription start sites. RT-PCR analysis led to the identification of this 5' end heterogeneity in different hematopoietic lineages. Discrepancies were particularly observed between B and T cells, due to an alternative splicing of one 5' exon (1b), which might be an important element in RhoH gene regulation. Such specific features have never been described for any Rho family member gene. They provide a molecular basis to study complex mechanisms involved in the control of RhoH expression.
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PMID:Structural features of hematopoiesis-specific RhoH/ARHH gene: high diversity of 5'-UTR in different hematopoietic lineages suggests a complex post-transcriptional regulation. 1556 31