Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 631-bp region of the long terminal repeat (LTR) of a variant of human T-cell lymphoma/leukemia virus type I (HTLV-I), isolated from a healthy member of a remote, recently contacted group (Hagahai) in Papua New Guinea, was sequenced and compared to LTR sequences of other members of the primate T-cell lymphoma virus group (PTLV), including HTLV-I, simian T-cell lymphoma virus (STLV-I) and HTLV-II. Sequence analysis of the LTR of this New Guinean isolate, designated as HTLV-I(PNG-1), indicated a sequence divergence of 8.4% to 10.4% from prototype Japanese HTLV-I(ATK) and other HTLV-I and STLV-I isolates and 48.6% diversity from HTLV-II. Few mutations were found in the core elements of the transcriptional enhancer regions, the TATA box promoter, and the polyadenylation signal and site. Further, the observed changes did not significantly alter the inferred stability of the Rex response element, a stem loop structure critical for polyadenylation and Rex protein binding. Dendograms based on LTR sequences indicated that the strain of virus that evolved into HTLV-I(PNG-1) diverged from the other PTLV in the distant past, just after the progenitors of STLV-I from Asia, but before the ancestors of STLV-I from Africa. By contrast, other HTLV-I isolates were found to represent strains of virus that have diverged more recently and clustered primarily according to their geographical origin. These data confirm that HTLV-I(PNG-1) is a new and distinct variant of the PTLV group. Also, our analyses suggest that both HTLV-I and STLV-I may have originated in the Indo-Malay region and eventually spread to Africa and then to the New World and Japan with horizontal transmission between man and nonhuman primates possibly occurring over thousands of years.
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PMID:LTR sequence and phylogenetic analyses of a newly discovered variant of HTLV-I isolated from the Hagahai of Papua New Guinea. 160 4

Therapy with interferon-alpha results in complete cytogenetic remission in 15-20% of patients with chronic myelogenous leukemia. Even during prolonged clinical follow-up, most of these patients do not relapse. However, because of the limited sensitivity of cytogenetic techniques (approximately 5%) and Southern blots (approximately 1%), it is uncertain whether the residual malignant clone becomes extinct or persists below the limit of detection in these patients. We used polymerase chain reaction to amplify the chimeric BCR-ABL transcripts in 18 patients with chronic myelogenous leukemia who became Ph1 chromosome negative while receiving treatment with interferon-alpha, either alone or in combination with interferon-gamma. At the time of study, these patients had been Ph1-negative for a median of 22+ months. Fifteen patients were positive for residual BCR-ABL transcripts. No residual BCR-ABL message was detected on analysis of multiple serial samples in three patients. In order to confirm these results, the samples from these three patients, along with positive and negative controls, were analyzed by two independent laboratories in a blinded fashion. In the first laboratory, RNA specimens from all three patients were considered negative using chemiluminescent acidinium-ester-labeled probes. In the second laboratory, samples from all three patients were also negative by conventional polymerase chain reaction (PCR). However, when a second round of amplification was carried out on the amplified samples using a different combination of primers, samples from two of the three patients were positive. The results confirm the presence of a small proportion of BCR-ABL-positive cells in the majority of patients who are in complete remission and highlight some of the potential problems of PCR-based analysis. There is a need to standardize PCR methodology and potential confounding factors need to be addressed before PCR can be generally applied to analysis of minimal residual disease in CML. The implications of BCR-ABL positivity for these patients are discussed.
Leukemia 1992 Aug
PMID:Minimal residual disease in interferon-treated chronic myelogenous leukemia: results and pitfalls of analysis based on polymerase chain reaction. 164 Jul 25

Pulsed field gel electrophoresis was used to construct a long-range map of the normal BCR gene. A single BssHII restriction fragment encompasses all the known exons of the BCR gene (except a small 5' part of exon one). MIuI has one restriction site within the first intron of the BCR gene and another 250 kb downstream. This MIuI fragment contains most of the BCR gene coding sequences apart from the first exon and contains more sequences downstream of the BCR gene than the BssHII fragment. The NarI restriction sites are very close to the BssHII sites in the BCR gene, but they differ in the ABL gene, so that NarI digests could theoretically provide additional information in chronic myeloid leukaemia (CML) patients. This map was used to confirm BCR gene involvement in two CML patients in whom results of conventional Southern blotting of DNA were ambiguous. It was also used in a third patient to demonstrate the presence of a breakpoint apparently outside the BCR gene. Preliminary evidence from the use of PFGE confirms the presence of three BCR-related genes homologous to 3' sequences in the classical BCR gene (BCR-1). These BCR-related genes are located at a considerable distance from BCR-1.
Leukemia 1991 Jul
PMID:Long-range mapping of the normal BCR gene. 164 56

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.
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PMID:Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction. 168 8

The Philadelphia chromosome defines chronic myeloid leukemia, and is mostly based on a translocation t(9;22) with a typical BCR-ABL rearrangement which also occurs in so called atypical translocations. The transformation of chronic myeloid leukemia is associated with clonal evolution in 80% of cases. The appearance of an isochromosome 17q unequivocally heralds the onset of a myeloid type of blast crisis. Treatment of Ph-positive CML has still to be considered palliative except for allogeneic bone marrow transplantation. The Philadelphia chromosome is also found in about 20% of patients with acute lymphoblastic leukemia and in about 2% of patients with nonlymphoblastic leukemia. It is associated with a poor prognosis. Molecular and cytogenetic findings help differentiating between de novo acute leukemia and blast crisis of chronic myeloid leukemia.
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PMID:[Cytogenetic and clinical features of Philadelphia chromosome positive leukemias]. 170 14

The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML is reflected by their reduced capacity to bind to marrow derived stromal layers in vitro. Whereas normal bone marrow Bl-CFC bind irreversibly to cultured stromal layers (and none are found in normal blood), the Bl-CFC in CML bind transiently and then detach. The normal cell adhesion mechanism is partially sensitive to treatment with phosphatidylinositol-specific phospholipase C (Pl-PLC), indicating the participation of a phosphatidylinositol (Pl)-linked structure; however, when CML cells were treated with Pl-PLC it had no effect on progenitor binding. Two other Pl-linked structures, decay-accelerating factor (DAF) and lymphocyte function associated antigen-3 (LFA-3) were normally expressed on CD34 positive CML cells and normally susceptible to Pl-PLC treatment. The treatment of normal cells with Pl-PLC, to mimic the situation in CML, resulted in the indiscriminate and inefficient binding of Bl-CFC to stroma. Moreover, treatment of the normal cells with 5637 conditioned medium (CM), which contains haemopoietic growth factors, also reduced the binding capacity of normal Bl-CFC; 5637CM treatment did not alter the expression of DAF. It is proposed that a Pl-linked cell adhesion molecule (CAM) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst, in normal cells, CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors.
Leukemia 1991 Aug
PMID:Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia. 171 60

Joining of the BCR and ABL genes is an essential feature of the group of human leukemias characterized by the Philadelphia chromosome and there is recent evidence that the human BCR-ABL fusion gene induces leukemia in experimental animals. Joining of these two genes is the result of cytogenetic translocation, usually the t(9;22)(q34;q11), but sometimes of more complex translocations involving one or more chromosomes in addition to chromosomes 9 and 22. The leukemic cells of some patients carry the BCR-ABL fusion gene but have an apparently normal karyotype. Recent studies show that these cells conceal complex chromosome rearrangements. Because the BCR-ABL fusion gene appears to be the result of cytogenetic rearrangement in all cases of these leukemias, the causes and mechanism of chromosome rearrangement will be relevant to the development of leukemia in man. We examine mechanisms of chromosome rearrangement and propose that both simple and complex chromosome translocations result from a single, though sometimes complex, interchange event.
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PMID:Complex chromosomal translocations in the Philadelphia chromosome leukemias. Serial translocations or a concerted genomic rearrangement? 175 91

To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.
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PMID:Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. 185 87

Sera obtained in 1987 from 63 male and 632 female Singapore prostitutes were screened for antibody to human T-cell leukaemia virus (HTLV)-I with a particle agglutination test. Of the 3 males and 4 females who were positive one had antibody to HTLV-I core and envelope antigen on Western Blot. Two subjects had presumptive antibody to HTLV-I core antigen and a third subject had such antibody on a repeat specimen in 1989. These sera were negative for HIV-1 antibody. There is evidence of infection with HTLV-I or a variant virus in this population. The infection is likely to have been sexually transmitted.
Int J STD AIDS
PMID:Evidence of HTLV-I infection in Singapore prostitutes. 186 47

A patient is described with de novo acute non-lymphocytic leukemia of megakaryoblastic lineage with tri-lineage myelodysplasia. This patient was studied cytogenetically and using molecular genetic techniques throughout her clinical course. She had an N-ras mutation at diagnosis which persisted despite a bone marrow transplant, and acquired a Philadelphia chromosome associated with a P190 BCR-ABL transcript at clinical relapse 3 months post-transplantation.
Leukemia 1991 Aug
PMID:Megakaryoblastic leukemia with an N-ras mutation and late acquisition of a Philadelphia chromosome. 188 21


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