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)

Recently, Molecular genetics has remarkably advanced and it is introduced in medicine. The use of recombinant DNA methods for the diagnosis of leukemias is reported with special reference to the contribution of cytogenetic findings, such as specific chromosome aberrations previously obtained. Therefore, cytogenetic studies on Ph1 chromosome and other specific aberrations found in leukemias are historically reviewed. Using Southern blotting, PFGE, PCR, and in situ chromosome mapping techniques we have analyzed many cases with CML and cases with ALL. We found M-bcr rearrangements not only in standard Ph1, but also in complex types and in Ph1 (-) ve CML. Chromosomal in situ hybridization was very informative identifying transposition of bcr and abl genes between chromosomes 22 and 9. In this connection, FISH (fluorescence in situ hybridization) technique was developed by us, which is expected to have an exceptional power of analysis. ALL had either M-bcr or m-bcr rearrangements, the latter being identified by PFGE. Next, application of PCR technique that enables to obtain more than 10(5) copies of target sequences could monitor minimal residual diseases in CML. Recently, the relevant gene were cloned respectively in FAB-M2 and APL (FAB-M3), so that detection of minimal residual diseases will be successfully performed in these types of leukemia. Finally, targeting chemotherapy using antisense sequences is prospectively described.
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PMID:[Advances in molecular genetic diagnosis of leukemia]. 181 42

This study was undertaken in order to estimate the incidence of leukemia among Koreans. Medical records were studied of patients with diagnoses of either ICD-9 038 (septicemia), or 204-208 (leukemias), or 284 (aplastic anemia), or 289 (other diseases of the blood and blood-forming organs) in the claims sent in by medical care institutions throughout the country to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987. These records were abstracted in order to identify and confirm new cases of leukemia among the beneficiaries of KMIC, which covers about 10% of the whole Korean population. Using these data from the KMIC, the incidence rates of leukemia among Koreans were estimated as of July 1st, 1986 to June 30, 1987. The crude incidence rate of all types of leukemia among Koreans is estimated to be 3.45 (95% CI; 0.77-9.55) and 2.29 (95% CI; 0.28-7.81) per 100,000 in males and females, respectively. The cumulative rate for the age span 0-64 is 0.25% in males and 0.18% in females, and for the age span 0-74, 0.35% in males and 0.23% in females. The adjusted rates for the standard world population are 3.90 and 2.48 per 100,000 in males and females, respectively. The relative frequencies by type are 51.5% for AML, 21.6% for ALL, 20.2% for CML, and only 1.5% for CLL. The incidence patterns of various types of leukemia, of which this is the first report in Korea, are analyzed and presented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Incidence estimation of leukemia among Koreans. 184 38

A combination of density flotation centrifugation and counterflow centrifugation (elutriation) allows the elimination of 98% of the T-lymphocytes, present in a marrow aspirate. This reduces substantially the occurrence of graft versus host disease (GvHD) after transplantation without loss of the repopulation capacity. A limitation of the traditional Beckman elutriator rotor is the relatively small size of the elutriation chamber, which makes five to six runs, of one hour each, necessary to process the whole bone marrow graft. We developed a new elutriator rotor, containing four disposable elutriator chamber (Dijkstra BV, Amsterdam, The Netherlands), which allows to complete the lymphocyte elimination from the bone marrow graft within 2 hours. Ninety-nine consecutive patients were transplanted with elutriated MLC-negative bone marrow grafts from histocompatible siblings. Indications for transplantation were: AML (n = 32), ALL (n = 34) and CML (n = 33). The grafts contained after counterflow centrifugation a mean of 12.1 (+/- 2.4)% of the nucleated cells, 1.9 (+/- 1.4)% of the T-lymphocytes, and 93.5 (+/- 59.4)% of the CFU-GM, originally present in the collected bone marrow. Immunoprophylaxis post grafting was given to 97 BMT recipients. Primary graft failure occurred in 5 of 95 evaluable patients (5%). The probability of acute GvHD greater than grade 1 at day 100 after BMT was 16%. The projected 3-year estimate of extensive chronic GvHD was 13%. The low incidence of GvHD was associated with a relatively low transplant related mortality in patients above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of graft-versus-host disease by lymphocyte depletion of the bone marrow graft with use of counterflow centrifugation. 186 51

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
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PMID:Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. 188 23

To investigate the possible role of the product of the retinoblastoma susceptibility gene, pRB, in leukemogenesis, we examined fresh leukemia cells from 56 cases of primary leukemia (AML, 32; ALL, 12; CML-BC, 9; CLL, 3) for expression of pRB by using an immunoblotting assay with anti-pRB monoclonal antibodies PMG 3-245 or 3-340. Expression of the 70 kDa heat shock protein (Hsp70) was examined simultaneously as an internal control. pRB was found to be absent or expressed at an abnormally low level in 13 of 56 cases. Abnormal expression of pRB was most common in AML (8/32) and CML-BC (4/9), and less common in ALL (1/12). Expression of pRB was not induced in two cases of pRB- AML cultured for 24 h with GM-CSF, indicating that pRB expression could not be induced by increasing the rate of proliferation. The eight cases of AML lacking pRB protein were examined for RB1 mRNA by Northern blot. Two lacked RB1 mRNA and six had a normal-sized mRNA (approximately 4.7 kb), although the amount of RB mRNA was very low in some cases. RB1 gene structure was normal by Southern blot in all eight cases lacking pRB protein which were studied. These results show that lack of pRB expression is relatively common in human myeloid leukemias, and suggests that loss of pRB expression could contribute to the altered growth control of these cells.
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PMID:Heterogeneous expression of the product of the retinoblastoma susceptibility gene in primary human leukemia cells. 188 10

We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.
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PMID:[Rearrangement and expression of bcr-abl genes in CML and ALL]. 189 Jul 38

Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes.
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PMID:Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. 190 97

In ALL the majority of cases possess clonal rearrangements of the Ig or TCR gene loci. Detection of these clonal markers by Southern blot analysis over a disease course has provided information on the fate and origin of leukaemic clones during treatment. Detection of these gene rearrangements has been used to detect residual disease during treatment. More recently, methods have been developed for the detection of Ig and TCR gene rearrangements using the polymerase chain reaction (PCR). This amplification technique allows for the rapid detection of gene rearrangements with a greater sensitivity than more conventional methods. The full impact and usefulness of this technique in residual disease detection has yet to be determined. The presence of the Philadelphia chromosome t(9;22) in ALL is associated with poor prognosis. Its detection by Southern blot is technically complicated due to the heterogeneity of chromosome breakpoints involved. The development of PCR-based methods for the detection of the bcr/abl mRNA associated with the Philadelphia chromosome has improved our understanding of the significance and incidence of this disease marker in ALL, emphasizing the importance of establishing Philadelphia status on all patients at diagnosis. Although longitudinal studies in CML have shown the presence of bcr/abl mRNA to be associated with residual disease, and its absence associated with long-term remission, these studies have yet to be reported for ALL. The usefulness of detection of residual disease using bcr/abl has yet to be determined.
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PMID:The molecular genetic analysis of gene rearrangements in acute lymphoblastic leukaemia. 195 87

A case of Ph1+ chronic myeloid leukemia in blast crisis (CML-BC) is reported, in which the periodic acid Schiff and myeloperoxidase negative blasts displayed high terminal deoxynucleotidyl activity and coexpressed both B- (CD19, CD10, and CD24) and T- (CD7) lymphoid markers. In line with the immunophenotype, DNA analysis revealed a rearranged configuration of both the immunoglobulin and T-cell receptor (beta, gamma, and delta) genes. In spite of this dual B/T phenotype and genotype, the negativity of CyCD3 favors the suggestion that the target of the neoplastic event is an early B cell, with a cross lineage involvement of the putative common recombinase. However, taking into account that a normal counterpart of a biphenotypic B/T ALL has been recognized, it could be hypothesized that the leukemic transformation may have involved an oligopotent B/T lymphoid precursor. This case confirms the lineage heterogeneity of CML-BC and suggests that DNA analyses coupled to extensive immunophenotyping may allow further insight for a more precise recognition of both normal and leukemic ontogenesis.
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PMID:Hybrid lymphoid blast crisis of chronic myeloid leukemia with both immunoglobulin and T-cell receptor gene rearrangements. 196 Jan 35

The expression of the multidrug resistance (MDR) phenotype is connected with the overexpression of P-glycoprotein. By applying the immunocytochemical assay we have demonstrated that in myeloproliferative diseases (AML, ALL, MDS, CGL), in single cases, in smear preparations from the peripheral blood and bone marrow the cells with MDR-positive phenotype can be detected in the material obtained from patients before therapy, and without clinically and anamnestically known exposure to cytotoxic or immunosuppressive drugs. This finding has demonstrated the presence of subpopulations of MDR-positive cells in leukemias and myelodysplastic syndromes already before therapy, and, furthermore, has evidenced that a positive MDR phenotype is not necessarily associated with a malignant phenotype of a malignant cell transformation.
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PMID:[Detection of cells with phenotype of multiple drug resistance in myeloproliferative disorders before the treatment]. 197 May 42


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