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)

We studied two cases of chronic myelogenous leukemia (CML) with unusual variant Philadelphia (Ph) translocation (22;22)(q11;q13). Southern blot analysis showed a chromosomal break in the BCR gene within the 5.8-kilobase (kb) breakpoint cluster region (bcr), between bcr exons 2 and 3 and between bcr exons 3 and 4, respectively. Chimeric bcr-abl mRNA was detected using polymerase chain reaction (PCR) which amplified, according to the respective bcr breakpoints, bcr exon 2-abl exon II and bcr exon 3-abl exon II junction products. These results further support the involvement, even when not cytogenetically detectable, of the 9q34 chromosomal region in all variant Ph translocations and that BCR-ABL gene fusion products are causally involved in the development of Ph positive CML.
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PMID:Chronic myeloid leukemia with unusual variant Ph translocation (22;22)(q11;q13). Two cases with chimeric BCR-ABL transcripts. 220 77

A proportion of cases of chronic myelogenous leukaemia (CML) has been described either (1) with a variant translocation, or (2) without the apparent involvement of both 9q34 and 22q11 (Ph-negative CML). All variant translocations have been further demonstrated to be complex implicating 9q34,22q11, plus another breakpoint on a variable chromosome. Complex translocations may be due to two successive events. Some of the breakpoints on the variable chromosome appear to be recurrent, and these remain to be studied for prognostic significance. Ph-negative CML comprises (1) cases of submicroscopic (hidden) insertion of 9q34-ABL within 22q11-BCR, and (2) cases without BCR-ABL rearrangement. We propose this last category to be called "CML-like disease", not to be confused anymore with true CML, and consequently to be studied as a separate entity.
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PMID:Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia. 222 45

The presence of Philadelphia chromosome t(9:22) is a hallmark of 95% of clinical cases of chronic myelogenous leukemia (CML) as well as 20% of adult acute lymphoblastic leukemia (ALL) and 5% of acute myeloid leukemia (AML). The product of t(9;22) is a fusion protein BCR-ABL. The fusion proteins of CML, ALL and AML have increased tyrosine kinase activity and show a transforming potential in vitro and in animal models. The shorter p190 protein is associated almost only with ALL and AML, while the protein p210 is present in both chronic phase and blast crisis of CML and also in 50% of Philadelphia-positive (Ph1+) ALL. In CML the transition from chronic phase to blast crisis is usually accompanied by additional genetic events, e.g. additional chromosomal abnormalities, and oncogene activation(s). The detailed understanding of molecular basis of CML, and Ph1+ ALL and AML provides highly sensitive molecular and serological methods to complement classical cytogenetics. The advantages and limitations of these techniques are described and discussed below.
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PMID:Molecular pathology of chronic myelogenous leukemia. 224 53

Double fluorescence in situ hybridization was used to detect Philadelphia (Ph) chromosomes in interphase nuclei and metaphases of patients with chronic myeloid leukemia. Application of cosmid probes for 3' ABL and 5' BCR sequences gave better results than libraries for chromosomes 9 and 22. The present approach may provide an alternative method for monitoring minimal residual disease in Ph+ CML patients.
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PMID:Detection of the Philadelphia chromosome in interphase nuclei. 226 53

Chronic myelogenous leukemia (CML) is characterized by the presence of a novel fusion gene comprised of portions of the BCR gene from chromosome (ch) 22 and the ABL gene from ch 9. The present study was designed to identify regulatory DNA regions as determined by DNAase I hypersensitivity to address the question of whether altered chromatin contributes to changes in ABL expression. We identify five hypersensitive (HS) sites within the abnormal BCR/ABL allele in K562 cells in a pattern different from the normal BCR. The pattern of hypersensitivity is modified when the cells undergo hemin induced differentiation. These results indicate that the normal BCR has a chromatin configuration consistent with active transcription and that the BCR/ABL fusion gene chromatin is different. This may be important in the pathogenesis of CML.
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PMID:Chromatin alterations surrounding the BCR/ABL fusion gene in K562 cells. 226 34

A patient with Philadelphia (Ph1)-negative, breakpoint cluster region (bcr)-positive chronic myeloid leukemia (CML) is reported. Pulsed-field gel electrophoretic analysis demonstrated the comigration of both ABL and BCR sequences on the same BssHII and SacII fragment. Moreover, in situ hybridization studies demonstrated that ABL sequences had been moved from band 9q34 to 22q11 and that the additional t(12;12)(q13;p12) was not involved in the ABUBCR related translocation. Nevertheless, a possible role of oncogenes or regulatory sequences activated or inhibited by the additional translocation cannot be excluded.
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PMID:Molecular and cytogenetic studies of a patient with Philadelphia-negative, BCR-positive chronic myeloid leukemia and t(12;12)(q13;p12). 227 60

We report on eight patients who were 35 to 77 years old with an isochromosome 17q as the sole structural chromosomal anomaly. Additional numerical chromosomal changes were a trisomy 8 or 17 in two cases each and a trisomy 19 in one case. Five patients had myelodysplastic syndrome (MDS) diagnosed according to the FAB nomenclature as chronic myelomonocytic leukemia (CMML) in two cases, refractory anemia with excess of blasts in transformation (RAEBt) in two cases, and refractory anemia with excess of blasts (RAEB) in one case. One patient suffered from a myeloproliferative disorder (MPS). All cases progressed to acute nonlymphocytic leukemia (ANLL) type M1, M2, or M4 in a period of 2 to 30 months after initial diagnosis, except one patient with RAEBt who died within 2 months. Two patients presented with ANLL-M2 at time of diagnosis. Treatment during the chronic phase of disease consisted of mild cytoreduction and/or substitution of platelets or red blood cells. One patient with CMML received an allogeneic bone marrow graft and relapsed after 33 months with ANLL-M1. Treatment results for overt leukemia were poor, and survival was short, lasting from 1 to 4 months. Overall survival was 1 to 37 months (median duration, 6.5 months). Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene, as observed in Ph1-positive chronic myeloid leukemia (CML). Thus, an i(17q) anomaly seems to identify a distinct subgroup of mostly myelodysplastic and, less frequently, myeloproliferative disorders that progress rapidly to ANLL, respond poorly to chemotherapy, and are associated with short survival after transformation.
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PMID:Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. 222 38

A patient who was diagnosed with chronic myeloid leukemia remained in chronic phase for 14 years before progressing into a lymphoid blast crisis in 1983. The acute phase was successfully treated, and the patient has remained in an indolent chronic phase to date. Cytogenetic and molecular analysis during this second chronic phase confirm the presence of the Philadelphia chromosome and its transcribed BCR-ABL mRNA. The breakpoint within M-bcr occurred in the 3' portion of the region and expressed a hybrid joining the b3 exon of BCR to the a2 exon of ABL.
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PMID:Molecular analysis of a CML patient with a long duration of chronic phase before and after lymphoid blast crisis. 235 47

Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. We prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. We used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment (median, 15 months; range, 6-45 months) and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. In 2 patients BCR-ABL mRNA was detected in all samples, and both have developed cytogenetic relapse. In 1 patient BCR-ABL mRNA was detected transiently during the first month after transplant but was undetectable thereafter. The fourth patient had BCR-ABL mRNA 6 months after bone marrow transplantation but not in prior samples. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. We recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.
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PMID:Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction. 240 84

We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.
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PMID:Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes. 248 42


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