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)

Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) can accurately detect and quantify cells with BCR/ABL fusion in <1% of 500 nuclei in 80% of patients with chronic myelocytic leukemia (CML) and t(9;22)(q34;q11.2). The remaining patients have one of three forms of atypical D-FISH patterns; these patterns have different sensitivities to detect disease. Neoplastic cells with one ABL, one BCR, and one BCR/ABL fusion are particularly problematic, because normal cells with coincidental overlap have the same pattern. For these patients, the normal cutoff for D-FISH is >23%. We tested a new method that incorporates an aqua-labeled probe for the argininosuccinate synthetase (ASS) gene into the conventional BCR/ABL D-FISH probe set. This tricolor D-FISH (TD-FISH) method takes advantage of the aqua-labeled ASS probe to distinguish between neoplastic and normal cells. We used TD-FISH to study 20 normal specimens and 35 specimens from 20 patients with known loss of both BCR and ABL from the derivative chromosome 9. The results show that TD-FISH effectively discriminates between cells with overlapping BCR and ABL signals from cells with true BCR/ABL fusion and improves the ability to quantify minimal residual disease from >23% to >1% of 500 interphase nuclei.
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PMID:A novel tricolor, dual-fusion fluorescence in situ hybridization method to detect BCR/ABL fusion in cells with t(9;22)(q34;q11.2) associated with deletion of DNA on the derivative chromosome 9 in chronic myelocytic leukemia. 1469 34

We report the case of a 57-year-old man who developed chronic lymphocytic leukemia (CLL) several months after the initial diagnosis of Philadelphia (Ph) chromosome-positive (Ph(+)) chronic myelocytic leukemia. CLL cells were purified by using fluorescence-activated cell sorting and further analyzed using interphase fluorescence in situ hybridization with probes to detect the BCR/ABL fusion gene. We provide evidence that the CLL cells arose in a Ph(-) clone.
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PMID:Chronic lymphocytic leukemia in the course of chronic myelocytic leukemia: evidence of independent clonal origin as shown by interphase fluorescence in situ hybridization and fluorescence-activated cell sorting. 1526 35

Erythroblast phase of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute erythroid leukemia are rare events. The distinction between these two entities is poorly defined. The World Health Organization (WHO) classification requires the presence of more than 50% of erythroblasts in the bone marrow for the diagnosis of both the erythroid/myeloid or pure erythroid subtypes of acute erythroid leukemia. However, in previous studies of erythroblast crisis CML, the percentage of erythroid series in the bone marrow is seldom mentioned and the direct relationship of the erythroblasts and the Philadelphia chromosome has never been established. We report a well-documented case of acute erythroid leukemia transformed from CML. The studies in morphology, immunohistochemistry, and flow cytometry fulfill the WHO criteria for the diagnosis of acute erythroid leukemia, and yet the complex karyotype containing Philadelphia chromosome indicates genetic evolution. Finally, the direct demonstration of the BCR/ABL fusion product by fluorescence in situ hybridization in the erythroblasts provides concrete evidence that the erythroblasts are part of the leukemic process and not an innocent bystander.
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PMID:Detection of BCR/ABL fusion product in normoblasts in a case of chronic myelogenous leukemia. 1531 26

Here we describe how we detected the BCR/ABL fusion gene on the short arm of der(9) combining classical GTG banding and Fluorescence In Situ Hybridization (FISH) in a case of chronic myeloid leukemia (CML). To our knowledge, variant translocations involving the short arm of chromosome 9, in literature, are almost rare in chronic myeloid leukemia. It is not clear if this complex genetic translocation represents clonal evolution or a unique, initial presentation variant of the Philadelphia chromosome (Ph).
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PMID:Complex variant Philadelphia translocation involving the short arm of chromosome 9 in a case of chronic myeloid leukemia. 1537 89

We report a 59-year-old man with chronic myelogenous leukemia (CML) in chronic phase who presented with a large abdominal tumor. Biopsy revealed proliferation of granulocytic-, erythroid-, and megakaryocytic-lineage cells in a retroperitoneal lymph node. The BCR/ABL fusion gene was detected on a paraffin-embedded tissue section of the lymph node by double-color fluorescence in situ hybridization, indicating an extramedullary hematopoietic tumor of CML origin. This patient has achieved a complete cytogenetic response for 19 months with imatinib mesylate (STI571; Gleevec), in association with the regression of the tumor. However, the development of an extramedullary tumor in chronic-phase CML generally indicates a poor prognosis, because it commonly consists of blast proliferation and is followed by blast crisis in the marrow within a few months. This case, therefore, points to the importance of histological examination of extramedullary tumors in CML for evaluation of disease status and for therapeutic decisions.
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PMID:Case of chronic-phase chronic myelogenous leukemia with an abdominal hematopoietic tumor of leukemic clone origin. 1538 5

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia chromosome (Ph) in more than 90% of cases. Recent studies using fluorescence in situ hybridization (FISH) have shown that in a subset of patients with CML, deletions of 9q34 involving the argininosuccinate synthetase region occur at the time of the Philadelphia translocation and are associated with a poor prognosis. We performed interphase FISH studies in 152 cases of CML using a dual-color, dual-fusion probe system with a third probe directed at 9q34. Cytogenetic studies showed a simple (typical) Ph in 124/152 (82%), a cryptic Ph in 11/152 (7%), and a variant Ph chromosome with a complex translocation in 17/152 (11%) of cases. Interphase FISH studies showed single BCR/ABL fusion patterns in 48/152 (32%) of cases. Deletions of 9q34 were observed in 14% of all the cases and were present in 46% of cases with single BCR/ABL fusion pattern. All the 9q34 deletions occurred in cases with single BCR/ABL fusion signal. However, a single-fusion pattern is not specific for 9q34 deletions, and cases should be routinely screened for the presence of this prognostically significant abnormality by using a third probe directed specifically at 9q34.
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PMID:Interphase fluorescence in situ hybridization studies for the detection of 9q34 deletions in chronic myelogenous leukemia: a practical approach to clinical diagnosis. 1547 49

The protein kinase Akt is activated in a wide variety of cancers, and this activation results in enhanced resistance to apoptosis through multiple mechanisms. This article reviews the control of Akt activation by the opposing actions of the oncogene phosphoinositide 3-kinase (PI3-K) and the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10. The activation of Akt by transforming mutations, such as the amplification of HER-2/neu in breast cancer and the formation of the BCR/ABL fusion gene in chronic myelogenous leukemia, seems to be essential for the transforming activity of these oncogenes. We discuss several of the proposed mechanisms for the antiapoptotic effect of activated Akt, including the inhibition of the proapoptotic protein Bad, downregulation of death receptors, and enhancement of the glycolytic rate. Increased glycolysis is seen in many malignancies and forms the basis for the increasing use of positron emission tomography imaging for diagnosis and staging. Finally, we discuss rapamycin and its analogs, which are now in trials as antineoplastic therapy; these agents show particular promise in tumors in which Akt has been activated.
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PMID:Putting the rap on Akt. 1548 33

Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of patients with CML, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated fetal liver kinase-1-positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of 17 Philadelphia chromosome-positive (Ph+) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single-cell level. These findings provide direct evidence for the first time that rearrangement of the BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of the BCR/ABL fusion gene in both blood and endothelial cells.
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PMID:Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics. 1559 Nov 20

The BCR/ABL fusion tyrosine kinase activates various intracellular signaling pathways, thus causing chronic myeloid leukemia (CML). Here we demonstrate that the inducible expression of BCR/ABL in a murine hematopoietic cell line, TonB210, leads to the activation of the Ras family small GTPase Rap1, which is inhibited by the ABL kinase inhibitor imatinib. The Rap1 activity in a CML cell line, K562, was also inhibited by imatinib. Inhibition of Rap1 activation by a dominant negative mutant of Rap1, Rap1-N17, or SPA-1 inhibited the BCR/ABL-induced activation of Elk-1. BCR/ABL also activated in a kinase activity-dependent manner the B-Raf kinase, which is an effector molecule of Rap1 and a potent activator of the MEK/Erk/Elk-1 signaling pathway. Together, these data suggest that, in addition to the well-established Ras/Raf-1 pathway, BCR/ABL activates the alternative signaling pathway involving Rap1 and B-Raf to activate Erk, which may play important roles in leukemogenesis.
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PMID:BCR/ABL activates Rap1 and B-Raf to stimulate the MEK/Erk signaling pathway in hematopoietic cells. 1559 48

The chronic myelogenous leukemia is a pluripotent hemopoietic stem cell disease characterized by the t(9;22) (q34;q11) reciprocal chromosomal translocation (Philadelphia chromosome). The translocation result the fusion of the ABL gene located at the long arm of chromosome 9 with the BCR gene located at the long arm of chromosome 22. The BCR/ABL fusion gene encodes a chimeric protein with elevated tyrosine kinase activity, that plays an important role in the pathogenesis of the disease. In the diagnosis of chronic myelogenous leukemia and in the evaluation of the therapeutic effect, the detection of the t(9;22)(q34;q11) translocation and BCR/ABL fusion gene plays an important role. The authors in the present paper provides a review on the recently used methods of the detection of t(9;22)(q34;q11) chromosomal translocation and BCR/ABL fusion gene and their role in the diagnosis, monitoring and evaluation of therapeutic effect in chronic myelogenous leukemia.
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PMID:[New approach in the diagnosis and monitoring of treatment in chronic myelogenous leukemia]. 1572 95


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