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

The purpose of this paper is to evaluate the possible clinical association of autoimmune thyroid disease and acute leukemia. This study is a retrospective review of all adult patients with acute leukemia treated at our institutions from 1978-1989. Those with both leukemia and thyroid disease were evaluated and are presented. Twenty-seven of eight hundred seventy patients with acute leukemia had evidence of thyroid disease. This is a 3-fold increase in overall incidence. Twenty-one patients had acute myeloid leukemia, five had acute lymphoid leukemia, and one had accelerated chronic myeloid leukemia. Thyroid disease entities included toxic multinodular goiter (four patients), idiopathic hypothyroidism (eight patients), Graves' disease (eight patients), and Hashimoto's thyroiditis (seven patients). Whereas the association may have had a negative effect on elderly patients, those with Graves' disease and Hashimoto's disease appeared to have an improved outcome of the leukemia. There is an increased association of autoimmune thyroid disease and acute leukemia. Since thyroid hormones are important regulators of hematopoiesis and utilize receptors similar to those of differentiating factors such as retinoids, the association may be important for further study of mechanisms of growth regulations in leukemia.
 ...
PMID:Association of thyroid disease with acute leukemia. 155 Jan 1

A patient with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) who was treated with alpha-interferon (alpha-IFN) is reported. After the treatment, the number of Ph+ bone marrow (BM) cells decreased gradually and the intensity of the rearranged major breakpoint cluster region (M-BCR) gene became faint; however, a lymphoblastic crisis developed about 1 year later. At the time of the blast crisis, the rearranged M-BCR band was detected, indicating that the blast crisis clone was derived from CML cells. The patient was treated with a combination of vincristine, prednisolone, daunorubicin, and L-asparaginase, and a hematologic remission was obtained. During the remission status, no rearranged M-BCR fragment was detected by conventional Southern analysis. Thus, the hematologic and genetic alteration in this case appeared to be identical to Ph+ acute leukemia with M-BCR rearrangement. The current case therefore indicates that alpha-IFN can reduce the proportion of Ph+ cells, but is unable to prevent blast crisis. Furthermore, the quantitative reduction of the cell population with a Ph chromosome may have some effects in modifying the genetic manifestations and clinical features of Ph+ CML, e.g., the delay in the appearance of the blast crisis.
 ...
PMID:Restoration of cytogenetically normal marrow cells after remission of lymphoblastic crisis in a case of Ph positive CML treated with alpha-interferon. 155 Oct 82

There is substantial evidence that the volume of medical procedures in a hospital has an inverse relationship with mortality. We analyzed data for 1313 recipients of HLA-identical sibling bone marrow transplants for early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in first chronic phase) to determine whether transplant outcome differed in small and large centers. Transplants were performed in 86 bone marrow transplant centers active between the years 1983 and 1988, which participated in the International Bone Marrow Transplant Registry. Twenty-one (24%) centers performed five or fewer allogeneic transplants per year during the study period; five (6%) performed more than 40 per year. After adjustment for differences in patient and disease characteristics, the relative risks of treatment-related mortality (1.53, P less than .01) and treatment failure (1.38, P less than .04) were higher among patients who received transplants at centers doing five or fewer transplants per year than among those at larger centers. Among patients receiving transplants in centers performing more than five transplants a year, there was no statistically significant correlation between number of transplants and outcome.
 ...
PMID:Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? 841 96

Lactoferrin is a member of the transferrin family of iron-binding proteins. It is found in several glandular epithelial tissues and human neutrophils, where it is localized to secondary granules. To examine the mechanisms controlling lactoferrin gene expression in neutrophils and defects in its expression in acute leukemia, we have cloned a lactoferrin cDNA from a chronic myelogenous leukemia library, and used it to obtain genomic clones representing the chromosomal lactoferrin gene. Using polymerase chain reaction, primer extension, and S1 analysis, we have identified the 5' end of the lactoferrin mRNA. We have defined a putative promoter region for the gene, and characterized its first two exons. In addition, we have examined the structure of these regions in DNA from HL60 cells. HL60 is a leukemic cell line that undergoes phenotypic neutrophil maturation on exposure to dimethyl sulfoxide (DMSO). However, the cells cannot be induced to express any secondary granule protein genes. We have shown that the 5' end of the lactoferrin gene, including the putative promoter region, is entirely normal in HL60. By Northern analysis, nuclear run-on studies, and primer extension assays we have shown that the gene is not transcribed in DMSO-induced HL60 cells. This supports the hypothesis that the defect in HL60 is an abnormality in the production or activity of a transacting regulator of lactoferrin gene expression.
 ...
PMID:Lactoferrin gene promoter: structural integrity and nonexpression in HL60 cells. 158 44

Activating ras mutations are frequent (25-60%) in chronic myelomonocytic leukemia (CMML) and in acute myeloid leukemia (AML) (30%), in contrast to chronic myeloid leukemia (CML) in which the incidence is very low (0-3%). This might reflect that the leukemic cell in CML is at a level of differentiation in which ras gene activation is not involved or, alternatively, might be due to the presence in CML of the bcrlabl fused gene. We have analyzed the presence of point mutations in codons 12, 13, 59, 61 and 63 of N-, K-, and H-ras genes, in 26 cases of Philadelphia-chromosome-positive, bcrlabl-positive acute leukemia (Ph+ AL), and in eight CMML cases by using the polymerase chain reaction. Aberrant ras genes were detected in a single Ph+ AL case, and in four out of eight CMML patients. The Ph+ AL showing altered ras allele had an unusual point mutation in H-ras gene, substituting leucine for glutamine. This mutation has not been previously found in any hematological disease. Our findings suggest that ras mutations are probably not involved in the pathogenesis of those leukemias in which blast cells contain bcrlabl oncogene activation.
 ...
PMID:Low frequency of ras oncogene mutations in Philadelphia-positive acute leukemia and report of a novel mutation H61 Leu in a single case. 158 96

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.
 ...
PMID:Second HLA-identical sibling transplants for leukemia recurrence. 160 Apr 15

Total body irradiation (TBI) and cyclophosphamide (Cy) is the conventional conditioning regimen for the patients who are to receive bone marrow transplantation (BMT). It is one of the most effective treatments for acute and chronic leukemias. In this paper we discuss the clinical and radiobiological features relative to TBI methods and to the kind of BMT. Graft-versus-host disease (GvHD) incidence is decreased by the depletion of T-lymphocytes from donor's bone marrow which causes high rates of rejection and relapses. Thus, more aggressive conditioning regimens are necessary than unmanipulated BMT. The results are also examined of different experimental and clinical trials on the immunohematological features of T-depleted BMT and the radiobiological behavior of normal and pathological target tissues due to different methods of TBI. We report the experience of the Perugia Bone Marrow Transplantation Unit and Radiation Oncology Service. We treated 54 patients suffering from acute leukemia (AL) and 34 cases with chronic myeloid leukemia (CML) with T-depleted allogeneic HLA-identical BMT. Three different conditioning regimens were employed in an effort to enhance cytoreduction and immunosuppression without significantly increasing extramedullary toxicity. TBI was administered according to a hyperfractionated scheme of 3 fractions a day for 4 days. The third conditioning regimen, including also thiothepa (TT), gave the best results in terms of stable uptake and leukemic cells eradication. Disease-free survival (DFS) is 55.5% in the patients with AL at a median follow-up of 40 months; in the patients with CML who were not treated with TT, DFS is 10% at a median follow-up of 60 months, while it is 66.6% at a median follow-up of 12 for the group of patients who received also TT. The conditioning regimen with hyperfractionated TBI, Cy and TT was effective and well tolerated; 12.5% of patients developed interstitial pneumonia.
 ...
PMID:[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations]. 160 3

For severe aplastic anemia and several malignant hemopathies allogeneic bone marrow transplantation is the only treatment with curative potential. This is the case for chronic myelogenous leukemia, the myelodysplastic syndromes and probably multiple myeloma and chronic lymphocytic leukemia. It seems also the best therapeutic option for young adults who suffer from acute leukemia and for whom an adequate family donor is available. We review here the main complications of the procedure. Their better knowledge and the way to prevent and to treat them has decreased the mortality and morbidity of this treatment which is mostly successful when applied on patients in the early phase of their disease. Recently, the availability of HLA typed registered volunteers has extended the applicability of allogeneic bone marrow transplantation for those patients who lack adequate familial donors.
 ...
PMID:[Bone marrow allograft in adults hemopathies. The Team of the Sterile Unit]. 160 90

Eight cases of Philadelphia positive acute leukemia (Ph+AL) were compared with 13 cases of Ph+ chronic myelogenous leukemia in blast crisis (BC) and 10 cases of Ph negative acute lymphoblastic leukemia (Ph-ALL) based on the clinical and molecular biological findings. Distinguishing clinical features were a high leukocyte count (median; 147.9 x 10(3)/microliters) for Ph+AL, and a high incidence of tumor formation and basophilia for BC. A cytogenetic study demonstrated the disappearance or marked reduction of Ph+ metaphases in Ph+AL in remission, while Ph+ cells persisted in BC. The major bcr gene was not rearranged in 4 Ph+AL cases, whereas it was found rearranged in 4 other cases of Ph+ AL and 6 cases of BC. Reverse transcriptase polymerase chain reaction technique demonstrated the presence of minor bcr/abl mRNA in the former three cases, and major bcr/abl mRNA in the latter 4 cases. Remission rates were 63% for Ph+AL, 38% for BC, and 100% for Ph-ALL, and the 50% survival were 12, 5 and 29 months, respectively. It was concluded that Ph+AL can be differentiated from BC by a marked reduction of Ph+ cells at remission, and that the prognosis of Ph+AL is better than BC, but worse than Ph-ALL.
 ...
PMID:[Clinical and molecular biological study of Ph positive acute leukemia: comparison with blast crisis of chronic myelogenous leukemia and Ph negative acute lymphoblastic leukemia]. 163 16

The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.
 ...
PMID:Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia. 168 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>