Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorescence in situ hybridization (FISH) and the reverse transcription-polymerase chain reaction (RT-PCR) were used to examine a patient presenting with acute myelogenous leukemia (AML) FAB M2, and a complex t(4;9;22)(p14;q34;q11.2). The patient's clinical course was characterized by an aggressive leukemia, resistant to intensive therapy including allogeneic bone marrow transplantation. FISH analysis, using two chromosome painting probes and a BCR/ABL specific probe, confirmed the cytogenetic observation of a 22q11.2-->4p14 and a 4p14-->9q34 exchange, and revealed the presence of a 9q34-->22q11.2, respectively. In addition, RT-PCR demonstrated the presence of a BCR/ABL transcript derived from the major breakpoint cluster region (M-bcr) of the BCR gene. This transcript has been shown to generate an active 210 kDa tyrosine kinase protein more commonly observed in chronic myelogenous leukemia. Because the presentation of AML with this ABL-->BCR fusion product is a rare event, it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4, 9, and 22 played a role in the aggressive presentation and clinical behavior of this patient's leukemia.
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PMID:Complex chromosome 4, 9, and 22 rearrangement in a patient presenting with AML-FAB M2. 907 96

The Norwegian Ministry of Health and Social Affairs recently introduced activity-based financing for hospitals partly based on diagnosis-related groups (DRG). We soon observed that there seemed to be a considerable discrepancy between the reimbursement amount and the real cost of allogeneic haemopoietic stem cell transplantation. It was therefore decided to undertake a prospective micro-cost analysis to define a more realistic reimbursement. To identify real costs, we undertook a registration of pre-transplant procedures, transplantation and 1 year follow-up costs, including harvesting, personnel costs, clinical and laboratory procedures, together with blood products and drugs related to patients and donors. These data were compared to hospital DRG reimbursement. This information was registered for 17 consecutive patients, with a mean age 40 years (range 17-58 years). Ten patients had chronic myeloid leukaemia, three had acute lymphatic leukaemia, two had acute myeloid leukaemia and two had myelodysplastic syndrome. The data analysis showed a mean cost of US$ 106825 (NOK 901982), (range US$ 42376-362430). The average actual hospital revenue (50% DRG reimbursement + income related to length of stay + special procedure funding) was US$ 36404 (range US$ 26228-55998). Activity-based financing as applied in Norway, under-compensates hospital costs for allogeneic bone marrow transplantation. The government should make realistic estimates of real costs before introducing financial reforms in the health care system.
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PMID:A prospective cost evaluation related to allogeneic haemopoietic stem cell transplantation including pretransplant procedures, transplantation and 1 year follow-up procedures. 1180 51

Chronic myeloid leukemia (CML) is a clonal disorder originating in the pluripotent hematopoietic stem cell (HSC), the hallmark of which is the constitutively activated p210-type of Bcr-Abl tyrosine kinase protein. Studies in recent years have helped us to understand the molecular processes involved in the initiation and progression of CML. Although a great amount of knowledge has been accumulated, the effect of Bcr-Abl on the HSC is still unclear. We have developed an in vitro system that mirrors the chronic phase of CML with a combination of in vitro embryonic stem cell differentiation and tetracycline-inducible Bcr-Abl expression. Enforced Bcr-Abl expression was sufficient to increase the number of both multilineage progenitors and myeloid progenitors. The current system is powerful for analyzing the genetic changes in hematopoietic development. This review focuses on how Bcr-Abl affects HSCs and how Bcr-Abl expression alters the properties of HSCs.
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PMID:Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells. 1213 93

A 58-year-old woman with chronic myeloid leukemia (CML), and previous intolerance to interferon was treated with the BCR-ABL tyrosine kinase protein inhibitor imatinib mesylate. Coincidentally, with the start of treatment, the patient developed acute renal failure, with acute tubular necrosis being observed on histopathology. Imatinib was stopped and three hemodialysis sessions were performed, which was followed by a progressive improvement of the renal function and normalization of the urine output. One year later the patient still has mild chronic renal failure and remains in chronic phase of CML on hydroxyurea treatment.
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PMID:Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia. 1291 79

We report here a 4-month-old child with a large, solid enhancing mass involving predominantly the suprasellar and diencephalic regions, with extension of both hemispheres. The patient underwent partial resection of the mass by right temporal craniotomy. Histological diagnosis was of a low-grade glioma consistent with pilomyxoid astrocytoma. Cytogenetic analyses revealed an insertion on chromosome 17 that involved disruption of the BCR gene. This finding suggests a possible rearrangement of this gene that could act in a similar way to chronic myeloid leukemia with formation of a chimeric tyrosine kinase protein. This study may suggest the use of inhibitors of tyrosine kinase proteins as an alternative treatment approach in cases of refractory or disseminated pilocytic astrocytomas.
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PMID:BCR gene disruption in a pilomyxoid astrocytoma. 1708 Jul 23

The Philadelphia (Ph) chromosome, a hallmark chromosomal anomaly observed in 95 percent of chronic myeloid leukemia (CML) cases, is known to involve the Abelson (ABL) proto-oncogene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22, producing BCR/ABL mRNA encoding an abnormal tyrosine kinase protein. In the process of generating BCR-ABL fusion, the deletion of residual BCR or ABL occurs in 15-30 percent of CML patients. In addition, some rearrangements are complex, and do not yield the ABL/BCR fusion due to the involvement of a third chromosome in the rearrangement. The possible role of these deletions and complex rearrangements in disease outcome is an ongoing topic of research. We report our results of cytogenetic analysis with GTG banding and fluorescence in situ hybridization using dual color dual fusion probe (D-FISH) from Vysis Inc, USA in 169 (109 male and 60 female) CML patients registered at The Gujarat Cancer and Research Institute (GC and RI) from April 2004 to December 2005. GTG banding was carried out in 123 cases having analyzable metaphases. Of these 123 cases, D-FISH revealed atypical signal patterns in 57 patients (46%), and 12 cases revealed additional complex translocations indicative of disease progression. Out of 57 cases with atypical FISH patterns, 22 included metaphase FISH results, and the rest had only interphase FISH performed. In addition to the hallmark Philadelphia chromosome, other chromosomal aberrations in CML revealed heterogeneity of molecular events. Pooling of more data may lead to identification of new CML sub-groups and hence help in the analysis of clinical trials. Patients enrolled in our prospective study of prognostic significance will be followed up for disease free and overall survival in correlation with ABL-BCR deletion status.
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PMID:Atypical D-FISH patterns of BCR/ABL gene rearrangements in 169 chronic myeloid leukemia patients. 1713 Jun 61

Imatinib (Gleevec) is currently the frontline therapy for chronic myeloid leukemia (CML), a disease characterized by the presence of a constitutively activated chimeric tyrosine kinase protein Bcr-AbI. However, drug resistance often occurs at later stages of the disease, principally because of the occurrence of mutations in the kinase domain. Second generation Bcr-AbI inhibitors, such as dasatinib and nilotinib are capable of inhibiting many imatinib-resistant forms of the kinase but not the form in which threonine is mutated to isoleucine at the gatekeeper position (T315I). In this study, we present the crystal structure of the kinase domain of the c-AbI T315I mutant, as well as the wild-type form, in complex with a pyrrolopyridine inhibitor, PPY-A. The side chain of Ile315 is accommodated in the AbI T315I mutant structure without large conformational changes proximal to the site of mutation. In contrast to other inhibitors, such as imatinib and dasatinib, PPY-A does not occupy the hydrophobic pocket behind the gatekeeper residue. This binding mode, coupled with augmented contacts with the glycine-rich loop, appears to be critical for its ability to override the T315I mutation. The data presented here may provide structural guidance for the design of clinically useful inhibitors of Bcr-AbI T315I.
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PMID:Crystal structure of the T315I mutant of AbI kinase. 1771 12

Chronic myeloid leukemia (CML) is a clonal disorder characterized by proliferation of hematopoietic cells that possess the BCR-ABL fusion gene resulting in the production of a 210 kDa chimeric tyrosine kinase protein. CML, when left untreated, progresses to a blast phase during which the disease turns aggressive and shows poor response to known treatment regimens. We have studied a Siddha herbal agent, Semecarpus anacardium Linn. nut milk extract (SA) for its antileukemic activity and its effect on the changes in energy metabolism in leukemic mice. Leukemia was induced in BALB/c mice by tail vein injection of BCR-ABL(+) 12B1 murine leukemia cell line. This resulted in an aggressive leukemia, similar to CML in blast crisis, myeloid subtype, confirmed by histopathological study and RT-PCR for the p210 mRNA in the peripheral blood, spleen and liver. Leukemia-bearing mice showed a significant increase in lipid peroxides, glycolytic enzymes, a decrease in gluconeogenic enzymes and significant decrease in the activities of TCA cycle and respiratory chain enzymes as compared to control animals. SA treatment was compared with standard drug imatinib mesylate. SA administration to leukemic animals resulted in clearance of the leukemic cells from the bone marrow and internal organs on histopathological examination and this was confirmed by RT-PCR for the p210 mRNA. Treatment with SA significantly reversed the changes seen in the levels of the lipid peroxides, the glycolytic enzymes, the gluconeogenic enzymes and the mitochondrial enzymes. These effects are probably due to the flavonoids, polyphenols and other compounds present in SA which result in total regression of leukemia and correction of the alterations in energy metabolism. Study of animals treated with SA alone did not reveal any adverse effects. On the basis of the observed results, SA can be considered as a readily accessible, promising and novel antileukemic chemotherapeutic agent.
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PMID:Restoration of energy metabolism in leukemic mice treated by a siddha drug--Semecarpus anacardium Linn. nut milk extract. 1835 58

Chronic myeloid leukemia is an incurable white blood cell disease with slow progression which affects myeloid stem cells. In the course of chromosome 22 shortening a fusion oncogene arises whose product, a Bcr-Abl oncoprotein, is a continuously expressed tyrosine kinase protein. Beside the opportunity of chemotherapy, stem cell therapy and interferon-a therapy, the application of tyrosine kinase inhibitors also became widespread in the treatment of the disease. Patients bearing the T315I point mutation, however, show resistance against all tyrosine kinase inhibitors, which can be managed by dose escalation or the combination of therapies. The discovery of RNA interference or gene silencing put the therapeutic opportunity of CML in new light. The in vitro application of anti-bcr-abl siRNA showed promising results in the causal treatment of the disease, feasible for identification of new genes associated to the disease, but we do not have sufficient evidence for the safety and efficacy of this method in human therapy.
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PMID:[New perspective in the treatment of chronic myeloid leukemia? gene silencing therapy]. 2240 58

Important advances in the understanding of the molecular basis of chronic myeloid leukemia have resulted in the development of new therapies and changed the paradigm for managing this myeloproliferative disease. Translocation of chromosomes 9 and 22 (known as the Philadelphia chromosome) results in a fusion BCR-ABL gene that produces a dysregulated BCR-ABL tyrosine kinase protein and triggers events leading to malignant transformation. The tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib block the BCR-ABL protein and prevent activation of the transformation pathways. Molecular monitoring, the most sensitive approach currently available to assess treatment response, measures BCR-ABL messenger RNA levels and serves as a surrogate marker of disease. Further, molecular responses are predictive of patient outcomes. It is important for advanced practitioners to become familiar with the technology and interpretation of molecular monitoring results as well as efforts to standardize this type of testing so they can educate their patients and aid their understanding of test results. Undetectable BCR-ABL levels can bring feelings of relief, whereas an increasing level can lead to anxiety. Advanced practitioners, therefore, are an important resource for interpreting results for patients, answering questions, alleviating concerns, and encouraging continued adherence to treatment.
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PMID:Interpreting molecular monitoring results and international standardization in chronic myeloid leukemia. 2503 41


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