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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylation of some genes is associated with tumoral progression in numerous cancers. The short arm of chromosome 11 is a hot spot for such methylations. The calcitonin gene (11p15) seems to be a good marker of these phenomenons, particularly in acute leukemias. The abnormal methylation pattern of the calcitonin gene in leukemic cells is visualized by Southern blotting after digestion of tumoral DNA with isoschizomeric restriction enzymes which are methylation sensitive or not. These studies seem of interest for acute myeloblastic leukemias (AML) where few molecular markers are available. Moreover hypermethylation of the calcitonin gene correlates with acceleration and transformation of chronic myeloid leukemia (CML). Sequential studies are warranted to evaluate if such techniques might help, especially for timing of bone marrow transplantation in CML.
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PMID:Hypermethylation of the calcitonin gene and leukemia. 181 14

The clinical aspects of disease progression in chronic myelogenous leukemia (CML) are well established, but the nature of the molecular events responsible is not known. We have previously reported a consistent pattern of novel sites of methylation in the 5' region of the calcitonin (CT) gene and other chromosome 11p loci in acute myelogenous and and lymphoid leukemias. In the present study, CT gene methylation patterns were investigated in peripheral blood from 51 patients with CML. Abnormal patterns were found in only 2 of 31 patients in chronic phase, but in 5 of 8 patients in accelerated phase, and in 11 of 12 patients in blast crisis (P less than .005). For one patient studied in blast crisis, abnormal CT gene methylation was found in the peripheral blast cells but not in the granulocytes. In two of three patients studied with CML and having normal peripheral cell patterns, abnormal patterns were found in marrow blast cells. In one patient, only partial normalization of the CT gene methylation pattern was seen after chemotherapy induction of a second chronic phase and the patient relapsed 5 months later. Our findings indicate that abnormal methylation of the 5' region of the CT gene is regularly a marker of disease progression in CML which may prove clinically useful. This abnormal methylation site is part of an imbalance in DNA methylation that may play a role in the progressive genetic instability which characterizes the advancing stages of CML.
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PMID:Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia. 203 23

Calcitonin gene methylation at CCGG sites were determined in 39 chronic myeloid leukemia patients by isoschizomeric restriction endonuclease analysis. A total of 27 patients were analyzed while still in the chronic phase: 20 patients had a normal gene, and seven had a hypermethylated gene. There were 12 patients initially studied in accelerated or blastic phases. All but one patient showed gene hypermethylation, suggesting a good correlation between gene methylation and disease stage. All five patients who, while still in the chronic phase, had a major 3.1-kb hypermethylated calcitonin gene fragment, accelerated within 2 to 27 months. In consecutively analyzed patients, the initially normal calcitonin gene changed to a hypermethylated state as the disease escalated. The hypermethylation predicted disease acceleration with a median lead time of 6 months before any morphologic or clinical signs of disease progression were seen. The disease progressed in 8 of 27 patients initially studied in the chronic phase: in only two patients this occurred without predictive methylation changes. The results suggest that the assessment of calcitonin gene methylation status may be a promising tool for monitoring chronic myeloid leukemia disease escalation.
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PMID:Acceleration of chronic myeloid leukemia correlates with calcitonin gene hypermethylation. 203 24

In a series of 59 patients with chronic or acute myelogenous leukemia (CML, AML) we investigated whether circulating immunoreactive human calcitonin (i-hCT) levels correlate with diagnosis, response to therapy and clinical course. I-hCT was detectable in plasma samples of 88% of patients with CML in the chronic phase and in 100% of patients with CML in blastic transformation. In the AML patients, a significant relation was observed between the cytological subtype and i-hCT levels at diagnosis. In sequentially studied patients the i-hCT plasma concentration was related to the overall mass of leukemic cells, being lower when complete remission was achieved than at diagnosis and increasing at time of recurrence. These data suggest that circulating i-hCT levels can serve as a "tumor marker" in human myelogenous leukemias.
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PMID:Immunoreactive calcitonin: a tumor marker for myelogenous leukemias. 223 Mar 49

An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms.
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PMID:Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies. 360 79

The incidence of elevated serum levels of immunoreactive calcitonin (CT) in human myeloproliferative and lymphoproliferative disorders was investigated. On the basis of twice the normal range, about 45% of patients with acute leukemia and blast crisis of chronic myelocytic leukemia (CML) showed elevated serum levels of CT. Markedly elevated levels (greater than 1,000 pg/ml) were only found in this group. Since immunoreactive CT dropped to normal or only slightly elevated levels in remission and increased again before or during relapse, serum CT levels seem to reflect the activity of the disease. However, in patients with chronic leukemia, Hodgkin's and non-Hodgkin's lymphoma, a lower incidence and only slightly elevated serum levels were found. In addition, the molecular weight of the proteohormone in serum specimen and cell extracts was investigated by gel chromatography. Besides physiological CT, different high-molecular weight forms of the hormone could be demonstrated in serum and in cell extracts. Extracts of leukemic cells revealed higher molecular forms only. It is suggested that the proteohormone is ectopically produced by leukemic cells.
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PMID:Ectopically produced calcitonin in human hemoblastoses. 712 Aug 75

Alterations in DNA methylation appear to be an integral part of the malignant transformation. For example, the p15 region of chromosome 11 with multiple genes related to cell growth regulation exhibits different methylation patterns in the 5' area of the calcitonin A gene in healthy bone marrow cells, and in leukemic cell populations. In this work the methylation status of the 5' area of the calcitonin gene in myeloproliferative disorders (MPD) other than chronic myeloid leukemia (CML) is studied. A total number of 37 patients with polycythemia vera, essential thrombocythemia, or myelofibrosis were studied. A control group of 18 healthy persons and patients with reactive hematologic changes was included. The DNA isolated from peripheral blood or bone marrow cells was digested with the methylation-sensitive HpaII restriction enzyme. A Southern blot was hybridized with a 1.7 kb probe specific to the 5' area of the calcitonin gene. The result was visualized autoradiographically and analyzed with a densitometer. The results have been expressed as ratios between the abnormal and normal autoradiography band intensities, referred to as the calc-value or CALC. An increase in the calc-value signifies increasing methylation. In the control group the calc-value had a mean of 0.274. The myelofibrosis patients exhibited very strong hypermethylation in the calcitonin gene 5' area, with a mean calc-value of 11.1 (median 2.6). The polycythemia vera patients showed considerable variation in their methylation status, with a mean value of 1.52. The essential thrombocythemia patients exhibited weak hypermethylation, with a mean calc-value of 0.58. A correlation between karyotypic abnormalities and hypermethylation was observed. Complicated forms of MPD exhibited higher levels of methylation than the uncomplicated disease forms.
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PMID:Calcitonin gene methylation in chronic myeloproliferative disorders. 830 47

The malignant diagnosis of a haematological disorder can in most cases be made by clinical signs and routine microscopic examination. However, it has become necessary to characterize the malignant clone with various markers, which give either knowledge of the prognosis of the disease or give tools for the laboratory follow up of the patient. In lymphatic diseases there are excellent markers of clonality. On the contrary in myeloid malignancies the few well characterized markers are mostly helpful in the clinical management of rare myeloid subgroups. The aim of our project has been to develop methods for laboratory monitoring of myeloid diseases by two major approaches 1) detection of methylation alterations in the short arm of chromosome 11 and 2) novel approaches for sensitive point mutation detection. The short arm of chromosome 11 has areas where the DNA becomes hypermethylated in acute leukemias and lymphomas. In this chromosomal area the calcitonin gene serves as a good marker for methylation alterations due to several CpG sites in the 5'area of the gene. Even if the gene is normally methylated in most cases of chronic myeloid leukemia (CML), we have found that the hypermethylation of the calcitonin gene marks progression of CML and precedes any other signs of acceleration with several months. The point mutations of certain proto-oncogenes, such as the N-ras gene, are attractive markers for detecting residual diseases after chemotherapy of high malignant haematological disorders. However, conventional methods for detecting point mutations have been both insensitive and cumbersome, and thus unsuitable for clinical routine laboratories. With the solid-phase minisequencing we can technically easily and accurately detect small quantities of mutated cells.
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PMID:Development of molecular genetic methods for monitoring myeloid malignancies. 832 16

It is well documented that the calcitonin gene area in the short arm of chromosome 11 is hypermethylated in most acute leukemias as well as in chronic lymphatic leukemia. In contrast, the gene is normally methylated during the chronic phase of the chronic myeloid leukemia but turns hypermethylated as the disease escalates. As the methylation of the calcitonin gene correlates with the disease activity in chronic myeloid leukemia, it seemed worthwhile to study the gene methylation in other premalignant hematologic conditions with a potential to terminate in fulminant acute leukemia. We report here on the calcitonin gene methylation in patients with myelodysplastic syndromes (MDS) using a methylation sensitive restriction enzyme HpaII and standard Southern blotting techniques. Bone marrow aspirates from a total of 26 MDS patients were studied. In 24 of these patients, the calcitonin gene was hypermethylated. There was no correlation between the methylation status and the morphological stage of the disease. All six patients with a blast count < 5% had a hypermethylated gene. Of the 19 patients with a blast count > 5%, 17 were hypermethylated only two having normal methylation status of the gene. It appears that the hypermethylation of the calcitonin gene area in the short arm of chromosome 11 may be an early event in the pathogenesis of the myelodysplastic syndromes. The methylation analysis may thus be of value as a diagnostic tool in MDS but an abnormal methylation pattern does not seem to have a direct relation with the degree of blast infiltration.
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PMID:Hypermethylation of the calcitonin gene in the myelodysplastic syndromes. 842 80

In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.
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PMID:Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients. 894 87


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