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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremendous advances in our understanding of acute leukemia have been made through the development of new technologies and close collaboration between immunologists, molecular biologists, and clinical oncologists. These technological advances have included the development of monoclonal antibodies (MoAb) reactive with surface antigens on leukemic cells which can help confirm the lineage and diagnosis of acute leukemia. More importantly, MoAb in conjunction with morphology and cytochemical stains have led to the identification of FAB-MO and the more common recognition of FAB-M7. MoAbs have also helped define prognostic groups, e.g., T-cell leukemia, mature B-cell leukemia, and rare groups such as CD7+ AML. However, the greatest advances in our understanding of acute leukemia has occurred with the application of genetic techniques. Disregulation of genes responsible for normal growth and differentiation initiates the molecular events that lead to the transformation and proliferation of cells recognized clinically as leukemia. Non-random cytogenetic abnormalities apparently contribute to this gene disregulation and specific abnormalities are associated with clinically important subgroups. In acute lymphoblastic leukemia (ALL), the t(9;22), t(1;19), and t(4;11) appear to have a poor prognosis. In acute myeloblastic leukemia (AML), -7/7q-;-5/5q-, 11q23 abnormalities have poor outcomes while t(15;17) and in some series t(9;11), t(8;21), and inv(16) have a good response to therapy. Molecular studies of somatic cell (immunoglobulin and T-cell receptor) gene rearrangements have assisted in the diagnosis and classification of ALL. The application of the polymerase chain reaction technique to specific gene rearrangements has provided a useful approach to minimal residual disease. Specific gene activation (N-myc, evi-1) or fusion genes such as the alpha retinoic acid receptor (alpha RAR) and pml have been identified as the specific cause of some cases of leukemia. The cloning of specific chromosomal breakpoints identified in leukemia (as has been done for CML) will result in specific probes which can be used to make the diagnosis rapidly at the molecular level. Because of the tremendous number of recent developments, this paper will focus only on major developments that will soon have a clinical impact.
Leukemia 1992 Nov
PMID:Pathology and immunology of acute leukemia. 143 16

Advances in molecular genetics in the past decade enabled us to analyze the cause of mendelian disorders at molecular level and a variety of mutations, not only in point mutations and deletion in exons but also in those occurred in regulatory elements or in RNA processing have been precisely identified. Such a variety of mutations may constitute variable clinical manifestations even in the simple mendelian disorders. On the other hand, pathogenesis of common diseases is much complicated and remains greatly to be elucidated. However, if we could use the strategies applied in the past few years for mendelian disorders, it seems to be not difficult to approach them. It is recommended to categorize a certain disease into subgroups for distinguishing their heterogenous phenotypes by clinical, biochemical and other properties. Owing to the success in making a subgroup (FAB classification), many subtype-specific translocations were found in leukemia, and then, rearrangement of relevant genes is also being shown. The best example is seen in chronic myelocytic leukemia. Since rearrangement of ABL and BCR was shown and both genes were cloned, detection of minimal residual diseases after intensive treatment became possible at 10(-6) level using RT-PCR technique. Recently developed interphase cytogenetics using FISH has visualized Ph1 translocation in metaphase cells and also in round nuclei, suggesting a potential use in monitoring the effect of certain drugs during treatment. Furthermore, very selective targeting therapy is being devised using antisense DNA.
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PMID:[Present status of gene diagnosis in cancer]. 144 79

We have performed a retrospective analysis of the clinical, morphologic, and cytogenetic findings in 26 patients diagnosed between January 1969 and September 1991 with acute erythroblastic leukemia de novo (EL or AML-M6). Clonal chromosomal abnormalities were found in 20 (77%) patients (95% confidence interval [CI], 61% to 93%). Loss of all or part of the long arm (q) of chromosomes 5 and/or 7 was observed in 17 (65%) patients (95% CI, 47% to 83%). In addition, the karyotypes were often complex, with multiple abnormalities and subclones. Among the remaining nine patients, six had a normal karyotype and one each had trisomy 8, t(3;3), or t(3;5). The overall frequency of abnormalities of chromosomes 5 and/or 7 observed in our M6 patients is similar to that observed in our patients with therapy-related acute myeloid leukemia (t-AML; 99 of 129 patients, 77%), but substantially higher than that noted in our other patients with AML de novo (French-American-British [FAB] subtypes M1-M5: 52 of 334 patients, 16%). Our M6 patients with abnormalities of chromosomes 5 and/or 7 were older and had a shorter median survival (16 v 77 weeks [P = .005]) than did the M6 patients without these abnormalities. We found no correlation between morphologic features and either cytogenetic abnormalities or clinical outcome. Of note was the finding that the percentage of myeloblasts, which may account for only a small fraction of the total marrow elements when the revised FAB criteria are applied, had no bearing on prognosis. We conclude that acute erythroblastic leukemia, when defined by morphologic criteria, consists of two distinctive subgroups: one group tends to be older, has complex cytogenetic abnormalities, especially of chromosomes 5 and/or 7, and shares biologic and clinical features with t-AML; the other group, with simple or no detectable cytogenetic abnormalities, has a more favorable prognosis when treated with intensive chemotherapy.
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PMID:Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. 145 Apr 12

In the present study fresh leukemic cells obtained from 23 patients with acute myeloid leukemia (AML; FAB subtypes: three M1, five M2, two M3, five M4, eight M5) were investigated for the membrane expression of the CD4 molecule by cytofluorimetric analysis with an anti-CD4 monoclonal antibody (mAb). In 15 cases the presence of the CD4 mRNA was also investigated using Northern blot analysis. Membrane expression of the CD4 molecule was demonstrated in 19 out of 23 cases, and it was found to be weaker than in CD4+ lymphocytes and monocytes obtained from normal controls. Full-length CD4 mRNA was detected in 12 out of 15 (80%) cases, and AML cells positive for CD4 mRNA expression also expressed the CD4 antigen. Since the CD4 molecule expressed by T cells is associated with p56lck, a member of the src family of intracellular tyrosine kinases, we investigated whether the CD4 molecule expressed by myeloid blasts is also associated with a tyrosine kinase activity. In vitro kinase assays performed on anti-CD4 immunoprecipitates from lysates of myeloid leukemia cells from four CD4+ cases were negative for the presence of a tyrosine kinase activity. This finding was not due to the lack of expression of members of the src family since we were able to detect at least p60src and p59fyn in myeloid leukemia cells. According to our results, the CD4 molecule seems to belong to the phenotypic repertoire of most AML, irrespective of their FAB subtypes. However, in myeloid blasts this molecule is not associated with a tyrosine kinase activity as it occurs in T lymphocytes.
Leukemia 1992 Dec
PMID:The CD4 molecule belongs to the phenotypic repertoire of most cases of acute myeloid leukemia. 145 71

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.
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PMID:CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex. 146 29

To investigate the role of retinoblastoma susceptibility (RB) gene inactivation in leukaemogenesis, we evaluated 36 bone marrow specimens of acute leukaemia for RB protein expression by immunoprecipitation and Western blot analysis. 15 patients had no detectable RB protein at initial screening. However, nine of them were subsequently excluded due to evidence of protein degradation. Of 27 valid cases, six (22%) were repeatedly shown to lack expression of the RB protein with three different anti-RB antibodies. Five were patients with acute myelogenous leukaemia (AML) and one, mixed-lineage acute leukaemia. The RB inactivation was noted more frequently in AML (5/18, 28%) than in acute lymphoid leukaemia (0/7, 0%). By karyotyping, none of these six patients exhibited cytogenetic changes involving chromosome 13q14, the RB locus. There is no correlation between inactivation of the RB gene and FAB subtypes or cytogenetic changes. Four patients achieved complete remission with standard chemotherapy for 6, 12, 20 and 26+ months, respectively. Southern and Northern blot analyses further indicated that the RB genes were grossly intact and the level of RB transcripts did not decrease in the majority of these six patients. These results suggest that the absence of RB products in some of acute leukaemia might be regulated at the post-transcriptional level, and it imposes no significant effect on treatment response and prognosis.
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PMID:Inactivation of the retinoblastoma gene in acute myelogenous leukaemia. 148 30

This report describes 2 patients who developed acute myelocytic leukemia (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy.
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PMID:Acute myelocytic leukemia and chronic myelomonocytic leukemia simultaneously with resectable breast cancer: a report of two cases. 149 12

Modern diagnosis and classification of leukemia are reviewed. The FAB (French, American, British) classification, introduced in the late 1970s has been the basis for most studies to date. During the 15 years since then, new categories such as M7 and M0 were added to the classification. The MIC proposal (morphology, immunology, cytogenetics) has been an important development which emerged from the knowledge about chromosomal changes and immunophenotyping. Improvement in diagnosis and classification will emerge from studies employing all the above techniques, including DNA analysis, in the 1990s.
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PMID:[Diagnosis and classification of leukemia]. 151 34

More detailed identification and understanding of the heterogeneity of leukemias using a broad panel of markers seems to be essential for the successful design of more sophisticated and effective treatments. Based on the FAB system, immunological phenotypes using a panel of monoclonal antibodies, and rearrangements of immunoglobulin and T-cell receptor genes, acute leukemia can be divided into six subtypes such as B-lineage, T-lineage, AML, NK-lineage, AUL and mixed lineage leukemia. The definition of B-lineage and T-lineage cells, a new classification for mixed lineage leukemia, incidence of dual rearrangements and their clinical significance are discussed.
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PMID:[Phenotypic and genotypic analysis of acute leukemia--current status of lineage specific classification]. 151 51

Myelodysplastic features of remission bone marrow were investigated in 46 adults with de novo acute myeloid leukaemia (AML) according to the FAB morphological criteria for myelodysplastic syndromes (MDS). Compared with a group of 18 patients with the common type of acute lymphoblastic leukaemia in remission, micromegakaryocytes (30.4% v. 5.6%, P less than 0.05), multi-separated nuclear megakaryocytes (45.7% v. 0%, P less than 0.01), degranulated neutrophils (39.1% v. 5.6%, P less than 0.05), and neutrophils with hyposegmented nuclei (34.8% v. 0%, P less than 0.01) were significantly more common in the AML patients. In contrast, dyserythropoietic changes had a similar incidence in both groups. When compared with the clinical features at initial diagnosis in AML cases, the dysmegakaryocytic changes in remission marrow were found to be significantly more frequent in patients with monocytic involvement (mainly M4) or trilineage myelodysplasia (T-MDS AML). Disease-free survival was significantly shorter in patients with micromegakaryocytes (P less than 0.05) or neutrophils with hypogsegmented nuclei (P less than 0.05) than in those without these features. Overall survival was also significantly shorter in patients with micromegakaryocytes (P less than 0.05). These findings may help in developing new strategies for the post-remission therapy of AML, and also suggest that myelodysplastic changes in the remission marrow of de novo AML patients may be related to haematopoietic recovery by a preleukaemic clone which eventually leads to early leukaemic relapse. Dysplastic marrow, however, was not necessarily associated with peripheral pancytopenia in the present series, warranting basic research on such putative clonal remissions.
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PMID:Remission with morphological myelodysplasia in de novo acute myeloid leukaemia: implications for early relapse. 152 Jun 22


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