Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridization with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34)inv(11)(q13q23). The rearrangement resulted in a 5'-MLL/FBP17-3' fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/FBP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a serial replating assay. Therefore, we assume that additional cooperating genetic abnormalities might be needed to establish a full malignant phenotype. FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe. Both domains are separated by a consensus Rho-binding motif that has been identified in different Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated whether FBP17 and members of the Rho family interact in vivo with a yeast two-hybrid assay. None of the various Rho proteins tested, however, interacted with FBP17. We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusion protein.
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PMID:The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia. 1143 82

We have identified two novel ABL1 fusion genes in two patients with B-cell acute lymphoblastic leukaemia (ALL) associated with a t(3;9)(p12;q34) and a t(5;9)(q23;q34), respectively. Molecular analysis revealed a FOXP1-ABL1 fusion for the t(3;9) and a SNX2-ABL1 fusion for the t(5;9). The fusions were confirmed by specific amplification of the genomic breakpoints using reverse transcription polymerase chain reaction. The identification of ALL with rare ABL1 fusion partners is important because the leukaemia may respond to tyrosine kinase inhibitors in the same way as ALL patients with a classical BCR-ABL1 fusion gene.
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PMID:Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia. 2139 72

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2-ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2-ABL1 fusion exhibited a BCR-ABL1+ ALL-like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype-based treatment stratification for patients with SNX2-ABL1 fusion.
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PMID:Poor responses to tyrosine kinase inhibitors in a child with precursor B-cell acute lymphoblastic leukemia with SNX2-ABL1 chimeric transcript. 2421 20

We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.
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PMID:Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1. 2436 93