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

In the present study we carried out allogeneic bone marrow transplantation (BMT) in 14 leukemia children with high risk prognostic factors. Six patients with acute nonlymphocytic leukemia (ANLL), four with acute lymphocytic leukemia (ALL), two with chronic myelogenous leukemia (CML), and two with myelodysplastic syndrome (MDS). Among these patients, six with ANLL, two with ALL, one with CML and one with MDS were alive in complete remission 8 to 58 months post-BMT. Four patients died of relapse (one with ALL, and one with MDS), and chronic GVHD (one with ALL and one with CML). In six patients recombinant granulocyte colony stimulating factor (rG-CSF) was used to shorten the period of granulocytopenia. The mean time of recovery to granulocyte count of 500/mm3 was 13.2 days in the rG-CSF+ group, being 15.9 days faster than that in the rG-CSF- group. In light of these results, allogeneic BMT is shown to be a choice of treatment for leukemia children with high risk prognostic factors and rG-CSF may be an effective reagent to prevent infectious episodes in BMT.
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PMID:Allogeneic bone marrow transplantation for malignant hematologic disorders in children. 128 58

A family with a high incidence of leukemia was investigated and followed up for 10 years. Up to now, 7 of 48 members in this family had acute nonlymphocytic leukemia. Chromosomal aberration was found in 3 healthy members, 2 of whom were found to have 47, XX, +5, -8, +Mar, del (7) (q22-qter) and 45, XO, -Y chromosomes and developed this disease 5 and 7 years later respectively. Pedigree analysis suggested that the hereditary defect in the family should rest on the maternal lineage. It is considered that hereditary factors play an important part in the pathogenesis of leukemia in the family.
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PMID:A study on a family with high incidence of leukemia. 129 Dec 2

The t(6;9) that characterizes a specific subtype of ANLL fuses the 3' part of a gene located on chromosome 9q34, CAN, to the 5' part of a gene located on chromosome 6p23, DEK. On the 6p- chromosome, the resulting DEK-CAN fusion gene is transcribed into a leukaemia-specific 5.5 kb chimaeric mRNA that encodes a putative DEK-CAN fusion protein. No transcription could be detected from the reciprocal CAN-DEK fusion on chromosome 9q+. Analysis of 17 t(6;9) ANLL cases showed that the translocation breakpoints occur in a single intron of 7.5 kb in the CAN gene (ICB9) and in a single intron of 9 kb in the DEK gene (ICB6). As a result, the presence of a t(6;9) in blood or bone marrow cells can be faithfully diagnosed by Southern blotting. Moreover, the result of the translocation is an invariable DEK-CAN transcript, which can be sensitively monitored by RNA-PCR. Surprisingly, a SET-CAN fusion gene was found in leukaemic cells from a patient with AUL. Like CAN, SET is located on chromosome 9q34, which explains the apparently normal karyotype of the leukaemic cells. The occurrence of a SET-CAN fusion gene indicates that CAN may be the relevant oncogene involved in leukaemogenesis, and that activation of CAN can be effectuated through fusion of its 3' part to either DEK or SET. As yet, the function of CAN, DEK or SET is unknown. None of the proteins shows consistent homology to any known protein sequences. However, preliminary localization data and analysis of sequence motifs suggested that DEK-CAN may have a role in transcription regulation. CAN contains several dimerization domains and a repeated motif that can function as an ancillary DNA-binding domain. DEK and SET are non-related proteins, but they share a stretch of acidic amino acids, which is also present in the fusion proteins.
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PMID:Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. 130 67

This paper reports for the first time results of cytogenetic studies on 14 consecutive secondary acute non-lymphocytic leukemia (S-ANLL) induced by bimolane therapy. They included 10 males and 4 females with ages ranging from 17 to 54 years. They had all suffered from psoriasis and received bimolane treatment before the occurrence of their leukemia. The total dose of bimolane ranged from 40 to 400 g (mean dose 194 g). The interval between the initiation of bimolane therapy and the diagnosis of leukemia was 12-96 months (median 30 months). A preleukemic phase was only found in one case. No dysplastic features in the hemopoietic series were seen in any patient. Chromosome analysis of bone marrow cells using banding techniques revealed clonal karyotypic abnormalities in all cases: t(15;17) in 8 cases of M3, of which 75% had extra abnormalities, t(8;21) in 4 cases of M2, del(7q) only in one case of M4 and one case of M5. After antileukemic therapy, complete remission was obtained in 10 out of 12 cases with specific translocations and one out of 2 cases with 7q-anomaly, respectively. The former survived 4-58 months (median 12 months), while the latter 1 and 9 months, respectively. This study indicates that: (1) bimolane is a causative factor of leukemia in this series; (2) the leukemia in our series is therapy-related leukemia (TRL) rather than de novo ANLL; (3) there exists, in fact, a new subgroup of TRL characterized by specific rearrangements, whose clinical, hematological and prognostic features and pathogenetic mechanism may be different from classical TRL characterized by chromosome abnormalities involving absence or deletion of parts of chromosome 5 and/or 7.
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PMID:Specific chromosomal translocations and therapy-related leukemia induced by bimolane therapy for psoriasis. 143 47

We describe a case of acute nonlymphocytic leukemia with inversion of chromosome 16 in a patient with systemic lupus erythematosus treated with immunosuppressive agents including azathioprine and cyclophosphamide. Although the leukemia may have been caused by other factors, it is worth noting the potential association of this malignancy with immunosuppressive therapy.
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PMID:Acute nonlymphocytic leukemia after treatment of systemic lupus erythematosus with immunosuppressive agents. 146 80

Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
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PMID:Expression of the Tn antigen in myelodysplasia, lymphoma, and leukemia. 147 Dec 47

The clinical utility of the indirect immunofluorescence (IF) and the alkaline phosphatase-anti-alkaline phosphatase (APAAP) techniques was compared in 103 newly diagnosed acute leukaemia patients immunophenotyped using a panel of 19 monoclonal antibodies (MoAb). In spite of slight variations in the percentages of cells reacting with particular MoAbs when comparing the two methods we found no discrepancies in the final classification of each case. In ANLL (n = 73) the best correlation between the two methods was found for CDw65 which is a good screening marker, and for CD15 having a prognostic significance. In ALL (n = 30) the best correlation was observed for CD19 and CD10, both of great diagnostic importance. The following antigens present both in membrane and in cytoplasm displayed higher positivity with the APAAP than in IF HLA-Dr, CD71 and CD11b in ANLL, CD22 and HLA-Dr in nonT-ALL and CD3 in T-ALL. The important advantages of the APAAP technique are: 1) its use with routinely performed bone marrow or peripheral blood films, which can be stored before staining, 2) the possibility of correlating morphology with immunological characterization and documentation of the results.
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PMID:[Comparison of clinical usefulness of immunophenotyping of leukemia using the immunofluorescence and immunoenzyme APAAP methods]. 148 65

Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made.
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PMID:Cytogenetic analysis in the diagnosis of acute leukemia. 151 24

A nationwide cooperative incidence survey of leukemia was carried out by the Institute of Hematology, CAMS, from 1986 to 1988. The cooperative survey network covered 46 investigating areas, involving 22 provinces, municipalities and autonomous regions. More than 60 million person-years were supervised and 1670 new cases identified. The annual incidence rate of leukemia was 2.76/10(5) and the 95% confidence interval of population rate ranged from 2.63/10(5) to 2.89/10(5). The incidence rates in oil fields and polluted areas were significantly higher than those in other areas. The incidence rate of ANLL was 1.62/10(5); ALL, 0.69/10(5); CML, 0.36/10(5); CLL, 0.05/10(5); and special types, 0.03/10(5). The incidence rate and constituent ratio of CLL were significantly lower than those in Europe and America. A peak of ALL incidence rate before age 10 was seen; this rate then declined with increasing age until 30. However, the incidence rates of other leukemia rose with age reaching peaks at old age (50-70). The leukemia rate in males was significantly higher than that in females, both in youth (10-29), caused by ALL, and at old age (greater than or equal to 60), mainly caused by ANLL. The incidence rates of ANLL subtypes (including M2b) are also reported.
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PMID:[Incidence survey of leukemia in China. Chinese Epidemiologic Study Group of Leukemia and Aplastic Anemia]. 153 78

The availability of an in vitro assay able to detect hematopoietic progenitor cells closely related to those responsible for marrow engraftment following autologous bone marrow transplantation (ABMT) prompted us to establish a procedure aimed at maximally increasing the concentration of the cyclophosphamide derivative mafosfamide used for marrow purging. It, therefore, was the aim of the present study to investigate in a group of patients with acute nonlymphoblastic leukemia (ANLL; n = 19) and acute lymphoblastic leukemia (ALL; n = 19) in complete remission the effect of mafosfamide at the level of adherent blast colony-forming units (blast colony-forming units, CFU-Blast), as well as multipotential (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM), erythroid (erythroid burst-forming units, BFU-E), and granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) progenitor cells. When nonadherent marrow mononuclear cells (MNCs) were incubated (30 min, 37 degrees C) with increasing doses of mafosfamide (30-120 micrograms/ml), a statistically significant (p less than or equal to 0.0005) dose-dependent suppression of CFU-Blast growth was observed. The mean (+/- 1 standard error of the mean [SEM]) values of 50% inhibition (ID50) of the CFU-Blast growth were not significantly different for ANLL (106 +/- 5) and ALL (107 +/- 5) patients. Analysis of CFU-Blast ID50 distribution demonstrated that ID50 ranged from 100 to 120 micrograms/ml in 17 cases (45%), whereas it ranged from 60 to 100 micrograms/ml in 12 cases and from 120 to 160 micrograms/ml in 9 cases. A statistically significant (p less than or equal to 0.05), dose-dependent suppression of colony growth from multi-potential and lineage-restricted progenitor cells was also observed. However, the value of CFU-Blast ID50 was significantly higher (p less than or equal to 0.05) than CFU-GEMM, BFU-E, and CFU-GM ID50 and ID95 values. In conclusion, our data demonstrate that: 1) the CFU-Blast assay allows to detect on an individual basis the doses of mafosfamide used for marrow purging, and 2) the concentrations of mafosfamide extrapolated by using the CFU-Blast assay are significantly higher than those obtained with the CFU-GM assay. The absence of any detrimental effect on marrow engraftment in vivo supports the safety of the CFU-Blast assay to evaluate the dose of mafosfamide used for marrow purging before ABMT.
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PMID:Differential sensitivity of adherent CFU-blast, CFU-mix, BFU-E, and CFU-GM to mafosfamide: implications for adjusted dose purging in autologous bone marrow transplantation. 156 48


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