Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have administered interferon alfa-2b, alone or in combination with chemotherapy, to 126 Ph1-positive chronic myelogenous leukaemia patients. Of 71 early chronic phase (CP) patients (less than 12 months from diagnosis), 41 (58%) obtained a complete haematological response (CHR). Daily interferon was more effective than intermittent administration. In previously untreated patients, the response was significantly influenced by risk status at diagnosis. Thirty-four out of 71 (48%) patients improved cytogenetically, the median of Ph1+ mitoses declining from 100% to 66% with complete Ph1-suppression in one case. Of 46 late CP patients (greater than 12 months from diagnosis), 32 (70%) achieved CHR with interferon alone or combined with chemotherapy. All 10 patients with disease well controlled by chemotherapy obtained stable CHR with interferon alone. Of 36 partial responders to conventional chemotherapy, 22 (61%) obtained CHR on interferon plus low-dose hydroxyurea. Ph1 mosaicism was reached by 16 (35%) late CP patients (median Ph1+ cells 75%). Of nine accelerated phase patients on interferon plus chemotherapy, one attained CHR, and two responded partially. At a median follow up of 36 months, of 41 CHR patients in early CP, 15 are controlled on interferon, 12 have had autologous bone marrow transplantation (BMT), and two allogeneic BMT. Blastic transformation (BT) has occurred in eight of 41 CHR patients (19%) versus 17 of 30 (57%) non-responders and partial responders to interferon. At a median follow up of 22 months, of 32 late CP patients obtaining CHR, 26 remain on interferon, one had allogeneic BMT, one had autologous BMT, and one developed BT (versus five out of 14 with less than CHR). These studies confirm the haematological and cytogenetic efficacy of interferon in CML and indicate that the disease status at the start of treatment is critical in determining the success of therapy.
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PMID:Evolving modalities of treatment with interferon alfa-2b for Ph1-positive chronic myelogenous leukaemia. 179 66

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

Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5-0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of AML subtypes by FAB classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors.
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PMID:Atomic bomb and leukemia. 182 51

The configuration of the T-cell receptor (TCR) beta, gamma and delta chain genes was analyzed in 16 cases of B-lymphoid blastic crisis of chronic myeloid leukemia (BC-CML) for a better definition of the biological aspects of this cellular population, in comparison with the molecular features of B-precursor acute lymphoblastic leukemia (ALL). All cases displayed B-phenotypic features, were Ph'-positive and had a rearranged configuration of the breakpoint cluster region (bcr) and of the immunoglobulin heavy chain gene region (JH). The TCR beta chain gene was rearranged in four cases (25%), all of which displayed a monoallelic rearrangement involving the J beta 2 region. The TCR gamma chain gene was rearranged in 13 cases (81%); 13 rearranged alleles utilized the J1/2 regions, while the remaining five utilized JP1. The V regions of the group I were mostly involved. The TCR delta chain gene was rearranged or deleted in 15 cases (94%); the 10 rearranged chromosomes displayed exclusively two patterns referable to partial recombinations, a V2-(D)-D3 and a (D)-D3 type. These two configurations are predominant in B-precursor ALL (75% of rearranged chromosomes) and almost absent in T-ALL. Taken together, these results document the close similarities between the genotypic features of B-lymphoid BC-CML and B-precursor ALL, not only in terms of the incidence of rearrangement but more relevantly with regard to the choice of regions involved in the recombinations. This aspect is particularly evident at the TCR delta locus level.
Leukemia 1991 May
PMID:Identical utilization of T-cell receptor gene regions in B-lymphoid blast crisis of chronic myeloid leukemia and B-precursor acute lymphoblastic leukemia. 182 53

The therapeutic efficacy and toxicity of alpha-interferon (alpha-IFN) (Roferon, Hoffmann-La Roche, Inc., Nutley, NJ) were determined in 15 children (age range, 6 to 20 years) with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML). All patients had received cytoreductive therapy with either hydroxyurea (n = 13) or busulfan (n = 1) or both (n = 1) for 6 weeks to 46 months (median, 7 months) before beginning alpha-IFN therapy at a dose of 5 x 10(6) U/m2/d intramuscularly. This dose was escalated to 10 x 10(6) U/m2/d if leukemia was inadequately controlled. Ten children had a hematologic response, with nine showing a reduction in the percentage of Ph+ marrow cells, including four who had no detectable Ph+ cells in marrow samples collected 48 to 204 weeks after the initiation of therapy. Two of 15 patients remain free of Ph+ cells. Therapy was discontinued before week 104 in ten patients because of the following: (1) early hematologic responses without a decrease in Ph+ cells (three patients); (2) early resistant disease (one patient); (3) blast crisis (one patient); (4) progressive disease (two patients); (5) seizure attributed to high-dose alpha-IFN (one patient); or (6) an inadequate trial of alpha-IFN caused by aseptic necrosis or poor compliance (two patients). The most common side effects were mild and have included fever, malaise, headache, myalgias, and pain at the injection site. Adverse events causing interruption of therapy were seizures, aseptic necrosis, and myelofibrosis. alpha-IFN stabilizes the chronic phase of Ph+ CML in some children, is adequately tolerated when administered at a dose of 2.5 to 5 x 10(6) U/m2/d intramuscularly, and results in a significant decrease in the proportion of Ph+ metaphases in some patients. alpha-IFN in combination with an effective cytoreductive agent or agents appears worthy of further clinical testing in this disease.
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PMID:Response to alpha-interferon in children with Philadelphia chromosome-positive chronic myelocytic leukemia. 183 44

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

Medical cost has increasingly become an important problem in the medical practice. As one of the useful fields of computer in the hospital, we have analyzed the costs of chemotherapy and bone marrow transplantation in patients with leukemia who were diagnosed between 1983 and 1986 and followed up till Dec. 1989. For CML the difference in the cost was 5 million yen and a survival rate was 75% and was higher in BMT than in chemotherapy. For Acute leukemia the difference of the costs was 8 million yen and survival rates were 89% and 30%. These data may show that BMT is a very effective and economical treatment for leukemia. In this study we have analyzed only the direct medical cost paid by the governmental insurance, however there seems necessary many other costs which are not covered by the insurance such as the cost for the family members, the cost for cryopreservation of cells and sterilization tentatively covered by the hospital or the cost of blood or marrow bank which are covered or should be covered by the government. Evaluation of the treatment outcome by the parameters such as length and quality of life, productivity of the patient, prevention of the loss of social investment including education on the patient, seemed also necessary for justification of the medical cost.
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PMID:[Cost of leukemia treatment]. 185 12

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

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

We report a patient with chronic myeloid leukaemia (Philadelphia-positive with M-BCR rearrangement) in transformation whose blast cells had myelomonocytic morphology, absent terminal deoxynucleotidyl transferase expression and non-lymphoid cell surface markers (CD10-, CD19-, CD33+, CD14+, CD11+). Leukaemia cell DNA showed rearrangement of both immunoglobulin heavy chain and T-cell receptor delta genes. Such rearrangements may be a feature of a small proportion of patients with non-lymphoid transformation of CML as they are in a minority of cases of de novo acute non-lymphoblastic leukaemia.
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PMID:Non-lymphoid blast crisis of CML with rearrangement of immunoglobulin and T-cell receptor delta genes. 190 27


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