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)

We report on a patient diagnosed with myeloid BC-CML in which a complete cytogenetic remission confirmed by FISH assay was obtained after therapy with carboplatin-ARA-C. However, RT-PCR analysis showed persistence of the p210 bcrabl translocation. Accordingly, the level of residual malignant cells should be between 10(-2) and 10(-6). Autologous stem cell transplantation was performed, but relapse occurred 11 months after blast crisis. This case supports the effectiveness of a carboplatin-ARA-C protocol in BC-CML in order to induce cytogenetic remissions.
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PMID:Complete cytogenetic but not molecular remission in a patient with myeloid blast crisis of chronic myeloid leukemia treated with carboplatin and ara-C. 940 33

Interferon-alpha (IFN-alpha) alone or in combination with cytostatic drugs can induce major and durable cytogenetic responses in about 20 to 25% of chronic myeloid leukemia (CML) patients. Since these patients have a significant survival benefit, more frequent follow-up investigations have become clinically important but require bone marrow (BM) aspirates. The aim of our study was to evaluate interphase fluorescence in situ hybridization (IPF) on peripheral blood (PB) smears as a rapid and reliable method to quantify Ph-positive myeloid cells. IPF analysis was performed on 49 PB samples from 36 patients in the chronic phase of CML and at different stages of cytogenetic remission. IPF results of 30 PB samples were compared with those from BM aspirates simultaneously obtained from the same patients to evaluate the correlation of Ph-positive cells. Further, the hypermetaphase FISH (HMF) technique was performed on cultured BM preparations of 31 patients for comparison with IPF results on PB. An excellent correlation was observed between the IPF results obtained on PB and BM samples (r = 0.98, y = x - 0.6, p < 0.0001). The mean difference between HMF from BM, on the one hand, and IPF from PB, on the other hand, was 3.2% (SD = +/- 8.4%). Seventy percent of samples were identically classified in one of the four subgroups of cytogenetic response. Thirty percent were classified in neighbouring response groups. We conclude that FISH performed on PB is a rapid and reliable method for assessing the cytogenetic response of CML patients on IFN-alpha based therapies, allowing more frequent and less invasive follow-up investigations although it is not able entirely to replace routine analysis of BM.
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PMID:Fluorescence in situ hybridization (FISH) on peripheral blood smears for monitoring Philadelphia chromosome-positive chronic myeloid leukemia (CML) during interferon treatment: a new strategy for remission assessment. 949 19

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 +/- 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-alpha2b (IFN-alpha2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6, 000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.
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PMID:Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. 955 93

There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.
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PMID:Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy. 963 1

The advent of molecular biological techniques has led to a radical improvement in the evaluation of haematological disorders and offers exciting future prospects. In particular it has led to the improved recognition of distinct clinicopathological entities defined by a combination of morphological, immunophenotypic and chromosomal features. Antibody-based techniques, namely immunophenotyping and immunocytochemical techniques, are essential to malignant haematological diagnosis. More novel is the diagnostic use of antibodies against novel fusion proteins, for example in AML, M3 and anaplastic lymphoma. PCR-based techniques allow the identification of genetic mutations and translocations including such common translocations as t(14;18), t(9;22), inv 16 and t(8;21). Fish-based techniques are greatly improving the ability to detect genetic abnormalities including those conditions with low cell proliferation and current research-based techniques include the combination of FISH with cell surface markers (FICTION), FIBRE FISH and Comparative Genomic Hybridization. Molecular techniques are essential in monitoring residual disease which is best illustrated in CML. The development of real-time automated PCR offers exciting prospects in this field. The increasing number of tests, the need for an integrated approach to diagnosis and the need for cost effectiveness indicate that such services should be provided by a specialized haematology laboratory.
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PMID:Modern molecular diagnostics and the management of haematological malignancies. 968 Dec 27

A 44-year-old man with CML in chronic phase was admitted for BMT from an HLA-identical sibling. Ph positive cells were undetectable at 3 and 7 months after BMT but became detectable by cytogenetic analysis of bone marrow aspirates at 12 months after BMT. He was treated with IFN-alpha (6 million units/day, 3 times a week) without apparent effect. Donor leukocyte transfusion (DLT) was performed four times between 20 months and 23 months after BMT, transfusing 3.4 x 10(8) mononuclear cells/kg. However, leukocytosis appeared and the NAP score declined at 25 months after BMT. FISH analysis revealed an increase in bcr-abl positive cells. IFN-alpha was restarted using the same schedule at 26 months after BMT. Three months after restarting IFN-alpha, the leukocyte count fell to the normal range, NAP score increased to a normal level, and bcr-abl positive cells decreased markedly. He has remained in hematological and cytogenetic remission for 20 months, and bcr-abl chimeric mRNA remained undetectable by PCR. These results suggest that CML which does not respond to DLT may be cured by subsequent IFN-alpha therapy, possibly by inducing anti-leukemia immune responses.
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PMID:[Successful treatment with donor leukocyte transfusion followed by interferon-alpha in a patient with relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation]. 969 73

The promyelocytic blast crisis is a rare form of transformation during the evolution of chronic myeloid leukaemia (CML). We report a case of promyelocytic blast crisis with t(15;17) in addition to t(9;22). The morphology and immunophenotype of the blasts were similar to those seen in acute promyelocytic leukaemia (APL). The t(15;17) was confirmed by FISH. The patient had evidence of coagulopathy with clinical and laboratory findings of disseminated intravascular coagulation (DIC). This report highlights the importance of correlating the results of multiple diagnostic methods in order to establish a correct diagnosis of the promyelocytic blast crisis of CML.
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PMID:Promyelocytic blast crisis of chronic myelogenous leukaemia with translocations (9;22) and (15;17). 972 Jul 33

The initial cytogenetic analysis of a biphasic synovial sarcoma showed an apparently normal karyotype. After FISH using chromosome X- and 18-specific probes and RT-PCR using SYT- and SSX-specific primer sets, a cryptic synovial sarcoma-associated t(X;18)(p11;q11) could be revealed. The "masked" nature of the translocation may best be explained by a two-step scenario in which a genuine t(X;18)(p11;q11) has occurred as a first step and a reverse reciprocal X;18 translocation as a second step, leaving the synovial sarcoma-associated SYT-SSX1 fusion intact. The findings further underline our previous suggestion that SYT-SSX1 fusions may correlate with a biphasic nature of the tumor. In addition, our findings indicate that, in analogy to, e.g., the Philadelphia translocation in chronic myeloid leukemia, "masked" translocations may occur in soft tissue tumors and that, as a standard, RT-PCR and/or FISH analyses should be carried out in order to provide karyotypic information that may be relevant to tumor diagnosis and/or prognosis.
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PMID:Masked t(X;18)(p11;q11) in a biphasic synovial sarcoma revealed by FISH and RT-PCR. 973 25

Using a highly sensitive fluorescence in situ hybridization method with probes for BCR and ABL1 (D-FISH), we studied 37 paired sets of bone marrow and blood specimens, collected within 24 to 96 hours of each other, from 10 patients before and during treatment for chronic myeloid leukemia (CML). The normal range for 500 interphase nuclei was </=4 (</=0.8%) nuclei based on 10 bone marrow and 10 blood specimens from normal individuals. The percentage of neoplastic nuclei was usually lower in blood than bone marrow. However, changes in the percentage of neoplastic nuclei in blood and bone marrow tracked closely over the course of therapy and with the results of quantitative cytogenetic studies on bone marrow. This result indicates that D-FISH is useful to test blood from patients with CML to monitor therapy. Moreover, by analysis of 6,000 nuclei with D-FISH, residual disease was identified in bone marrow and blood for patients in complete cytogenetic remission. Consequently, D-FISH analyses of interphase nuclei from blood could substitute for Q-cytogenetic studies on bone marrow. Thus, it may not be necessary to collect bone marrow samples so frequently to monitor therapy in CML.
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PMID:A special fluorescent in situ hybridization technique to study peripheral blood and assess the effectiveness of interferon therapy in chronic myeloid leukemia. 974 69

Clinical, morphological, cytogenetic and molecular (fluorescence in situ hybridization and RT-PCR) data were analyzed in twelve Philadelphia negative chronic myeloid leukemias (Ph-negative CMLs). Four patients were classified as BCR-positive. A standard b2a2 or b3a2 transcript was found, and the BCR-ABL hybrid gene was located on the 22q11 band in three cases and on the 1p35 band in one case with a t(1;9)(p35;q34). All were classified as typical chronic granulocytic leukemia (CGL) according to the French-American-British (FAB) morphological guidelines. Responses to therapy were evaluated by FISH in the four patients, and proved to be poorer than in Ph-positive CMLs. Eight BCR-negative patients were identified. They could be characterized by an older age, a less proliferative form of disease than the BCR-positive patients, and a frequent (six out of eight) abnormal karyotype. The FAB classification identified four CGLs and four atypical CMLs (aCML). A normal karyotype was more frequent in the patients classified as CGL whereas all the aCMLs had a chromosomal abnormality. Three patients had chromatin clumping and this morphologic feature was associated with trisomy 8 in two. No correlation between the cytogenetic, morphologic and the clinical data were found. Five patients had poor tolerance to therapy with a frequent occurrence of bone marrow failure and hemorragic syndrome, whereas three patients responded to a standard treatment of CML. Our study reinforces previous data on Ph-negative BCR-positive CMLs and emphasizes the difficulty in correlating clinical, morphologic, cytogenetic data in Ph-negative BCR-negative CMLs. However, our data also argue in favor of the existence of true Ph-negative BCR-negative CMLs and suggest that some of them can respond to a standard treatment of CML.
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PMID:Clinical, morphological, cytogenetic and molecular aspects of a series of Ph-negative chronic myeloid leukemias. 976 19


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