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Lancet (London, England) May 1971
Topics: Acute Disease; Adolescent; Age Factors; Boston; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid
PubMed: 4102980
DOI: No ID Found -
Journal of Clinical Pathology Feb 1985This report summarises the current knowledge regarding the clinical utility of biochemical enzyme markers for both diagnostic and therapeutic purposes in acute... (Review)
Review
This report summarises the current knowledge regarding the clinical utility of biochemical enzyme markers for both diagnostic and therapeutic purposes in acute leukaemia. The enzymes studied most extensively in this field are terminal deoxynucleotidyl transferase, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, and acid phosphatase, esterase, hexosaminidase isoenzymes. For each enzyme, the quantitative and qualitative characteristics in various immunologically defined subclasses of acute leukaemia are described. The quantitative evaluation of enzyme activities represents an adjunctive classification technique which should be incorporated into the multivariate analysis, the "multiple marker analysis." By qualitative characterisation pronounced heterogeneity of leukaemia subsets is uncovered. The application of 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase, and the potential usefulness of two other enzymes as targets for treatment with selective agents is discussed. The concept that gene products expressed at certain developmental stages of normal cells can similarly be detected in leukaemic cells (which therefore seem to be "frozen" or "arrested" at this particular maturation/differentiation stage) is supported by the results obtained in enzyme studies. Besides their practical clinical importance for classification and treatment of acute leukaemias, biochemical enzyme markers constitute a valuable research tool to disclose biological properties of leukaemic cells.
Topics: 5'-Nucleotidase; Acid Phosphatase; Acute Disease; Adenosine Deaminase; DNA Nucleotidylexotransferase; Enzyme Inhibitors; Esterases; Hexosaminidases; Humans; Leukemia; Leukocytes; Nucleotidases; Phenotype; Purine-Nucleoside Phosphorylase
PubMed: 2981904
DOI: 10.1136/jcp.38.2.117 -
The Lancet. Oncology Sep 2010The process of malignant transformation in paediatric acute leukaemias is complex, requiring at least two deleterious events resulting in DNA damage. This damage ranges... (Review)
Review
The process of malignant transformation in paediatric acute leukaemias is complex, requiring at least two deleterious events resulting in DNA damage. This damage ranges from point-mutations to double-strand DNA breaks leading to various types of chromosomal rearrangements. In this review we summarise the most common genetic aberrations for the three main subtypes of paediatric acute leukaemia: B-cell-precursor acute lymphoblastic leukaemia, T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Several genetic aberrations are independent prognostic factors, and are now used in risk stratification for treatment. Molecular pathways activated by genetic aberrations could provide potential molecular targets for novel therapies. Some genetic aberrations represent sensitive targets for molecular detection of minimal residual disease. This provides hope for the development of targeted therapies, effective against leukaemic cells.
Topics: Cell Transformation, Neoplastic; Child; Chromosome Aberrations; Humans; Leukemia
PubMed: 20435517
DOI: 10.1016/S1470-2045(09)70369-9 -
British Journal of Haematology Jan 2020Acute myeloid leukaemia (AML) is a blood cancer characterized by acquired genetic mutations. There is great interest in accurately establishing measurable residual... (Review)
Review
Acute myeloid leukaemia (AML) is a blood cancer characterized by acquired genetic mutations. There is great interest in accurately establishing measurable residual disease (MRD) burden in AML patients in remission after treatment but at risk of relapse. However, inter- and intrapatient genetic diversity means that, unlike in the chronic myeloid and acute promyelocytic leukaemias, no single genetic abnormality is pathognomonic for all cases of AML MRD. Next-generation sequencing offers the opportunity to test broadly and deeply for potential genetic evidence of residual AML, and while not currently accepted for such use clinically, is likely to be increasingly used for AML MRD testing in the future.
Topics: Hematologic Neoplasms; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Promyelocytic, Acute; Neoplasm, Residual
PubMed: 31804716
DOI: 10.1111/bjh.16362 -
Hematopathology and Molecular Hematology 1996Although morphology and cytochemistry continue to be the mainstay of the diagnosis of acute leukemia (AL), new developments in immunophenotyping, cytogenetics, molecular... (Review)
Review
Although morphology and cytochemistry continue to be the mainstay of the diagnosis of acute leukemia (AL), new developments in immunophenotyping, cytogenetics, molecular biology, and in vitro assays have dramatically improved our understanding of this disease and enabled the identification of entities with distinct clinico-biologic features. Immunophenotyping is essential for diagnosing and subclassifying acute lymphoblastic leukemia (ALL) and is also very helpful in certain types of acute myeloid leukemias (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings are clinically relevant for diagnosis and prognosis. Nonrandom chromosomal abnormalities such as t(15;17)(q22;q12) or t(1;19)(q23;p13) have been so closely associated with distinct types of acute leukemias that their recognition can allow diagnosis independent of the other criteria. Molecular analysis is a powerful method in the assessment of the malignant potential, clonality, and classification of the ALs. It has become clear that in some leukemias a proportion of patients exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand apparently uniform chromosomal abnormalities such as the t(1;19), t(9;22), t(8;14), or t(15;17) may differ at the molecular level. In vitro assays can evaluate the growth pattern and cell-cycle kinetics of leukemic cells, as well as their sensitivity to therapeutic agents. All these data are relevant to the management of AL. Because the French-American-British (FAB) classification does not fully correlate with much of this new information, alternative classifications have been proposed. In this review we concentrate on recent diagnostic contributions resulting from advances in biotechnology and discuss some of the points that arouse controversy in the single classifications.
Topics: Acute Disease; Biotechnology; Histocytochemistry; Humans; Immunophenotyping; Karyotyping; Leukemia; Leukemia, Myeloid; Microscopy, Electron; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 8792146
DOI: No ID Found -
Hematology/oncology Clinics of North... Dec 2011From the standpoint of the hematopathologist, attempts to dissect the immunophenotype and other lineage-defining characteristics of the puzzling group of acute leukemias... (Review)
Review
From the standpoint of the hematopathologist, attempts to dissect the immunophenotype and other lineage-defining characteristics of the puzzling group of acute leukemias of ambiguous origin have prompted considerable discussion and debate. For clinicians, however, such definitions, although academically interesting, as yet give relatively little insight into the most appropriate therapy, and patients with MPAL continue to do poorly compared with more typical AML or ALL cases. The most recent WHO 2008 MPAL definitions are provocative, but represent a major change from the previous EGIL BAL classification, and the clinical relevance of this change has yet to be established. Only further insight from the molecular biology laboratory can help define the true cell of origin and molecular drivers of ambiguous leukemias. New molecular information will allow clinicians and pathologists to refine classification of these challenging entities, and most importantly, should permit improved treatment for patients.
Topics: Acute Disease; Cell Lineage; Humans; Leukemia; Phenotype
PubMed: 22093585
DOI: 10.1016/j.hoc.2011.09.014 -
British Journal of Haematology Oct 2013Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and... (Review)
Review
Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and adverse outcome. According to World Health Organization 2008 classification, ALAL encompasses those leukaemias that show no clear evidence of differentiation along a single lineage. The rarity of ALAL and the lack of uniform diagnostic criteria have made it difficult to establish its cytogenetic features, although cytogenetic analysis reveals clonal chromosomal abnormalities in 59-91% of patients. This article focuses on the significance of cytogenetic analysis in ALAL supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow up and treatment selection of ALAL. It reviews in detail the types of chromosomal aberrations, their molecular background, their correlation with immunophenotype and age distribution and their prognostic relevance. It also summarizes some novel chromosome aberrations that have been observed only once. Furthermore, it highlights the ongoing and future research on ALAL in the field of cytogenetics.
Topics: Age Factors; Chromosome Aberrations; Cytogenetics; Humans; Immunophenotyping; Leukemia, Biphenotypic, Acute; Prognosis; Research; Treatment Outcome
PubMed: 23888868
DOI: 10.1111/bjh.12484 -
Orvosi Hetilap May 1990Results of morphological, cytochemical and immunological studies performed in adult acute leukaemias have been compared. Thirty one cases proved to be acute myeloid... (Review)
Review
Results of morphological, cytochemical and immunological studies performed in adult acute leukaemias have been compared. Thirty one cases proved to be acute myeloid leukaemia, while 25 cases were shown to be acute lymphoid leukaemia. Based on our results we conclude that immunophenotyping with monoclonal antibodies does not help in distinguishing the subtypes of AML. For purposes of clinical diagnosis cytochemical methods are valuable. On the other hand the monoclonal antibodies are essential in distinguishing the very immature myeloid and lymphoid leukaemias and this is of great importance from the clinical point of view, in determining therapy. Moreover, the diagnosis of acute lymphoid leukaemias is not possible without the specific monoclonal antibodies. Their application is first of all in haematological centers caring for leukaemia patients nowadays already obligatory. Gene rearrangement studies make the diagnosis more accurate and help in the diagnosis of leukaemias of unknown immunological origin.
Topics: Adult; Antibodies, Monoclonal; Female; Gene Rearrangement; Humans; Immunohistochemistry; Leukemia, Myeloid, Acute; Leukemia, T-Cell; Male; Phenotype; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 2194149
DOI: No ID Found -
Recent Results in Cancer Research.... 2008In summary, the management of women diagnosed with leukaemia in pregnancy needs an interdisciplinary approach, including a careful oncological work-up as well as close... (Review)
Review
In summary, the management of women diagnosed with leukaemia in pregnancy needs an interdisciplinary approach, including a careful oncological work-up as well as close monitoring of the pregnancy until delivery and beyond. Patients with acute leukaemias normally must receive anti-leukaemic treatment at full dosage prior to delivery, except for selected women diagnosed very close to term. Treatment should be avoided in the first trimester. The prognosis of pregnant women with acute leukaemia corresponds to that of an age-matched and diagnosis-matched non-pregnant cohort of patients, provided appropriate treatment is given. If given as of the second trimester, the typical chemotherapy regimes used for acute leukaemias imply acceptable acute toxicities to the fetus, with a somewhat increased risk of premature birth or developmental retardation, but no clear evidence of late sequelae in children and adolescents who were exposed to cytostatic agents whilst in utero. In chronic leukaemias and MDS, treatment may often be delayed until after delivery. In CML targeted therapy with imatinib mesylate is safe as of the second trimester, and possibly even before. Obstetric care and monitoring of women with leukaemia are essential throughout the pregnancy to ensure the best possible outcome for mother and child.
Topics: Female; Humans; Leukemia; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 18080447
DOI: 10.1007/978-3-540-71274-9_10 -
Advances in Experimental Medicine and... 2014Acute leukaemias are a group of malignancies characterised by the invasion of the bone marrow by immature haematopoietic precursors and differentiation arrest at various... (Review)
Review
Acute leukaemias are a group of malignancies characterised by the invasion of the bone marrow by immature haematopoietic precursors and differentiation arrest at various maturation steps. Multiplicity of intrinsic and extrinsic factors influences the transformation and progression of leukaemia. The intrinsic factors encompass genetic alterations of cellular pathways leading to the activation of, among others, inflammatory pathways (such as nuclear factor kappa B). The extrinsic components include, among others, the inflammatory pathways activated by the bone marrow microenvironment and include chemokines, cytokines and adhesion molecules. In this chapter, we review the role of inflammatory processes in the transformation, survival and proliferation of leukaemias, particularly the role of nuclear factor kappa B and its downstream signalling in leukaemias and the novel therapeutic strategies that exploit potentially unique properties of inflammatory signalling that offer interesting options for future therapeutic interventions.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Humans; Inflammation; Inflammation Mediators; Leukemia; Macrophages; Signal Transduction
PubMed: 24818729
DOI: 10.1007/978-3-0348-0837-8_13