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)

A characteristic feature of chronic myeloid leukaemia is that in 95 per cent of cases bone marrow cells manifest the Philadelphia (Ph1) chromosome. Treatment for cure includes allogenic bone marrow transplantation, but owing to the age factor and the lack of compatible donors this alternative is only available to a minority. Attempts to reduce or eliminate the Ph1-positive clone have been successful in the short term. Results from current trials with alpha-interferon (leukocyte interferon) show that when instituted during the chronic phase the treatment produces complete remission and cytogenetic response in 70 per cent of cases. The side effects are manifest, however, and it remains unclear whether alpha-interferon treatment prolongs the chronic phase.
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PMID:[Interferon treatment in chronic myeloid leukemia]. 154 56

Treatment with recombinant human interferon alpha-A (Roferon-A) is associated with stable suppression of the population of cells that display the Philadelphia (Ph1) chromosome in some patients with chronic myelogenous leukemia (CML) as defined by cytogenetic analysis. Southern blot analyses employing a 3' breakpoint cluster region (bcr) probe (Pr-1) were performed to confirm a complete suppression of the Ph1+ chromosome-positive clone of cells at the DNA level. The complete disappearance of rearranged restriction fragments of the bcr gene, which were a characteristic of the disease prior to Roferon-A therapy, was accompanied by the restoration of normal bone marrow and achievement of durable ongoing complete remission for 9 and 6 months, respectively, in two patients with Philadelphia-positive (Ph1+) CML. Molecular analysis is a valuable probe for monitoring the clinical course of disease in patients with Ph1+ CML.
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PMID:Molecular analysis of interferon-induced suppression of Philadelphia chromosome in patients with chronic myeloid leukemia. 288 Jun 16

Fourteen patients with chronic myelogenous leukemia were treated with partially pure leukocyte interferon (HuIFN alpha). The binding of recombinant leukocyte clone A IFN and the induction of 2',5'-oligoadenylate synthetase (2,5A) in peripheral blood cells were studied to determine whether they correlate with clinical response to IFN therapy. The mean pretherapy binding of radiolabeled recombinant leukocyte clone A IFN to peripheral blood cells was 0.053 +/- 0.02 (SE) fmol (53 +/- 20 amol)/10(6) cells and 0.049 +/- 0.015 fmol/10(6) cells in sensitive and resistant patients, respectively. Twenty-four h after the first HuIFN alpha dose, the binding of recombinant leukocyte clone A IFN decreased 3- to 8-fold in both sensitive and resistant patients. The activity of 2,5A synthetase was induced approximately 100-fold in sensitive patients from a pretherapy mean of 3 +/- 2 nmol/mg to a maximum of 317 +/- 184 nmol/mg during therapy. In contrast, 2,5A synthetase was induced from a pretherapy mean of 0.9 +/- 0.9 nmol/mg to only 6.7 +/- 4.9 nmol/mg in resistant patients. In two patients originally sensitive to HuIFN alpha who developed resistance to therapy, receptors were present in both sensitive and resistant disease stages and appeared to down regulate with therapy regardless of response. In these two patients, 2,5A synthetase was significantly induced with therapy in the sensitive stage but not in the resistant stage. This study shows that lack of clinical response to interferon therapy may coincide with failure to induce 2,5A synthetase activity. This suggests that resistance to alpha-interferon therapy may be mediated by events beyond receptor binding resulting in a failure to induce enzymes responsible for mediation of interferon antiproliferative effects.
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PMID:In vivo sensitivity and resistance of chronic myelogenous leukemia cells to alpha-interferon: correlation with receptor binding and induction of 2',5'-oligoadenylate synthetase. 294 42

T cells from the peripheral blood of patients with chronic myeloid leukemia (CML) were cultured with phytohemagglutinin and T-cell growth factor (TCGF) in agar culture. These T-cell colonies were pooled and expanded further in liquid culture with TCGF and then simultaneously analysed for the E-rosette receptor with the monoclonal antibody OKT11 and for the presence of the Philadelphia (Ph1) chromosome. OKT11 analysis showed these populations to be composed 99.5% or more of T cells. In four of the seven patients the T-cell suspension showed 7/50 (14%), 3/36 (8%), 2/34 (6%), and 4/44 (9%) Ph1 metaphases. Furthermore, Ph1 metaphases were demonstrated in T-cell cultures in two patients when bone marrow metaphases simultaneously showed 90 and 100% Ph1 negative metaphases secondary to human leukocyte interferon therapy or combination chemotherapy. A minority of T cells in benign phase CML have the Ph1 abnormality despite reduced number of Ph1 metaphases in bone marrow from therapy.
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PMID:T-cell involvement in benign phase chronic myelogenous leukemia. 309 99

A patient with Philadelphia-chromosome positive chronic myelogenous leukemia developed interferon antibodies on treatment with recombinant interferon alpha-2b. Clinically this event corresponded with progressive disease. No cross-reactivity of antibodies with human leukocyte interferon was found by Western blot. Treatment was switched to human leukocyte interferon with an obvious clinical effect: WBC was reduced and platelet count stabilized, but the effect was transient and no hematologic remission was achieved. Human leukocyte interferon may be an alternative in CML-patients with neutralizing antibodies to recombinant interferon alpha.
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PMID:Treatment with natural human interferon alpha of a CML-patient with antibodies to recombinant interferon alpha-2b. 319 82

Myeloid cytoreduction leading to hematologic remissions is frequently seen among patients with chronic phase Philadelphia-positive chronic myelogenous leukemia (CML Ph') treated with leukocyte interferon (IFN-alpha). In order extend our understanding of the events associated with interferon-induced myeloid cytoreductions, we have examined the changes in granulocyte-monocyte colony-forming cells (GM-CFC) in such CML Ph' patients. A total of 28 CML Ph' patients in hematologic remissions following IFN-alpha treatment had a median GM-CFC of 12 (range, 0-182)/1 X 10(5) bone marrow cells. This was significantly lower than the median GM-CFC of 104 (range, 44-815; p less than 0.01) in 22 untreated or minimally treated CML Ph' patients and the median of 72 (range, 30-204; p less than 0.05) in 18 normal controls. A gradual decline in the GM-CFC numbers from a median of 105 to a median of 1.8 was seen in six responding patients who were studied serially over a median period of 7.5 months. In these patients, we also observed a profound decline in the number of aspirated bone marrow nucleated cells and a decline in the bone marrow cellularity. The effect of treatment interruption for a median of 13 days was studied in five patients. In three of the patients who had received IFN-alpha for less than or equal to 6 months, treatment interruption resulted in rapid increase in the GM-CFC, while the GM-CFC did not change in the remaining two patients, who received IFN-alpha for one and two years. We conclude that treatment of CML patients with IFN-alpha resulted in a progressive decline of the bone marrow GM-CFC. The initially expanded pool of committed myeloid stem cells declines gradually, and at the time of hematologic remission the number of GM-CFC/10(5) nucleated bone marrow cells is lower than that of normal controls. In the early phases of IFN-alpha treatment, this inhibitory effect is rapidly reversible, but it seems to persist when the treatment is extended over more than one year.
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PMID:Changes in granulocyte-monocyte colony-forming cells among leukocyte-interferon-treated chronic myelogenous leukemia patients. 346 Aug 11

Inhibitory effects of two human interferon preparations, leukocyte interferon (Le-IF) and fibroblast interferon (F-IF), on granulocytic progenitor cells (CFU-C) from hematologically normal cancer patients and from patients with chronic myelogenous leukemia were evaluated. There was a wide variation in sensitivity of CFU-C to both Le-IF and F-IF. F-IF was mor inhibitory against CFU-C than le-If. Normal CFU-C and chronic myelogenous leukemia CFU-C were equally inhibited by both interferons. Effects of both interferons were neutralized by corresponding specific antisera but not by the other antisera. These observations confirmed that differences in immunogenicity of the interferons may attend their different origins.
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PMID:Inhibitory effects of human leukocyte and fibroblast interferons on normal and chronic myelogenous leukemic granulocytic progenitor cells. 617 Sep 21

We investigated the antiproliferative effect of partially purified human leukocyte interferon (HuIFN-alpha) given in a dose of 9-15 X 10(6) U daily by intramuscular injection to 7 patients with chronic myelogenous leukemia (CML). Hematologic remission of the disease was obtained in 5 patients. Among the responding patients, the mean white blood cell count decreased from 97.4 X 10(3)/cu mm (range from 35 X 10(3)/cu mm to 239 X 10(3)/cu mm) to 4.2 X 10(2)/cu mm (range from 3.0 X 10(3) to 7.9 X 10(3) cu/mm). Parallel reduction occurred in serum B12, from a mean of 1,435 pg/ml to a mean of 726 pg/ml, and lactate dehydrogenase levels, from a mean of 325 mU/ml to 112 mU/ml. Enlarged spleens decreased in 3 of 3 patients. The 5 responding patients have been maintained on HuIFN-alpha, 3 X 10(6) U daily or every other day, for 6+-35+ wk.
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PMID:Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. 619 58

Nine patients with refractory chronic myelogenous leukemia and severe symptomatic thrombocytosis (greater than or equal to 1 X 10(6) platelets/mm3) were given partially purified human leukocyte interferon-alpha. A significant decline in platelet counts, from a mean (+/- SE) of 1.71 +/- 0.53 X 10(6)/mm3 to a mean of 0.52 +/- 0.24 X 10(6)/mm3 (p less than 0.01), resulted in all patients. Maintenance of low platelet counts was achieved in two patients for more than 143 and 300 days, respectively. Treatment with human leukocyte interferon-alpha was stopped in the remaining patients because of increases in the leukocyte count, toxicity, or both. Our preliminary observations suggest that human leukocyte interferon-alpha may significantly alleviate progressive thrombocytosis in advanced chronic myelogenous leukemia. Further studies of human leukocyte interferon-alpha and chemotherapeutic agents are indicated.
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PMID:Human leukocyte interferon to control thrombocytosis in chronic myelogenous leukemia. 658 Aug 36

The results of the treatment with lymphoblastoid alpha interferon (IFN-alpha N1) in 10 patients with chronic myeloid leukaemia who had poor response to previous recombinant alpha interferon (rIFN-alpha) are presented. Eight of these patients had not developed anti-alpha 2 interferon antibodies, and 2 had non-neutralising anti-IFN antibodies. Three of the 10 patients received benefit from IFN-alpha N1 treatment. Two of them, with no response to rIFN alpha 2, attained complete haematologic response wit IFN-alpha N1. Cytogenetic responses although minimal, were achieved as well. The third patient, after receiving rIFN-alpha for 3 years with no response, had partial cytogenetic response after 4 months of treatment with IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN alpha 2 without anti-IFn alpha 2 neutralising antibodies may be useful in a minority of patients, although the frequency of cytogenetic responses is low.
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PMID:[Treatment with lymphoblastoid alpha interferon in patients with chronic myeloid leukemia refractory to recombinant interferon alpha 2]. 986 41


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