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CA: a Cancer Journal For Clinicians 1994Major advances in the diagnosis, classification, and treatment of adult acute leukemias have resulted in significant increases in the number of complete remissions and... (Review)
Review
Major advances in the diagnosis, classification, and treatment of adult acute leukemias have resulted in significant increases in the number of complete remissions and long-term disease-free survivors. Despite these improvements, most adult patients with acute leukemias still eventually die from their disease or complications of its treatment. New experimental and clinical approaches used to diagnose, monitor, and treat these diseases hold promise for further increased cure rates in the future. This article reviews the classification, immunobiology, cytogenetics, diagnosis, and treatment of adult acute leukemias and describes new directions being taken toward their cure.
Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Humans; Leukemia
PubMed: 7953914
DOI: 10.3322/canjclin.44.6.326 -
Archives of Pathology & Laboratory... Jan 2011Timely and accurate diagnosis of hematologic malignancies is crucial to appropriate clinical management. Acute leukemias are a diverse group of malignancies with a range... (Review)
Review
CONTEXT
Timely and accurate diagnosis of hematologic malignancies is crucial to appropriate clinical management. Acute leukemias are a diverse group of malignancies with a range of clinical presentations, prognoses, and preferred treatment protocols. Historical classification systems relied predominantly on morphologic and cytochemical features, but currently, immunophenotypic, cytogenetic, and molecular data are incorporated to define clinically relevant diagnostic categories. Multiparameter flow cytometry provides rapid and detailed determination of antigen expression profiles in acute leukemias which, in conjunction with morphologic assessment, often suggests a definitive diagnosis or a narrow differential. Many recurrent molecular or cytogenetic aberrations are associated with distinct immunophenotypic features, and therefore flow cytometry is an important tool to direct further testing. In addition, detection of specific antigens may have prognostic or therapeutic implications even within a single acute leukemia subtype. After initial diagnosis, a leukemia's immunophenotypic fingerprint provides a useful reference to monitor response to therapy, minimal residual disease, and recurrence.
OBJECTIVE
To provide an overview of the application of flow cytometric immunophenotyping to the diagnosis and management of acute leukemias, including salient features of those entities described in the 2008 World Health Organization classification.
DATA SOURCES
Published articles pertaining to flow cytometry, acute leukemia classification, and experiences of a reference flow cytometry laboratory.
CONCLUSION
Immunophenotypic evaluation is essential to accurate diagnosis and classification of acute leukemia. Multiparameter flow cytometry provides a rapid and effective means to collect this information, as well as providing prognostic information and a modality for minimal residual disease evaluation.
Topics: Acute Disease; Disease Management; Flow Cytometry; Humans; Immunophenotyping; Leukemia; Leukemia, Myeloid, Acute; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 21204710
DOI: 10.5858/2010-0387-RAR.1 -
Seminars in Diagnostic Pathology Aug 2003Because of the increasing recognition of the importance of genetic events to the diagnosis and treatment of the acute leukemias, the proposed new World Health... (Review)
Review
Because of the increasing recognition of the importance of genetic events to the diagnosis and treatment of the acute leukemias, the proposed new World Health Organization (WHO) classification incorporates genetic aberrations and immunology as major defining features in addition to morphology. In a hierarchal approach, genetic changes have precedence in the acute myeloid leukemias and immunology and genetic changes have precedence in the acute lymphoblastic leukemias. Four major groups of acute myeloid leukemia are recognized: 1) Acute myeloid leukemias with recurrent genetic abnormalities, 2) Acute myeloid leukemia with multilineage dysplasia, 3) Acute myeloid leukemias, therapy related, and 4) Acute myeloid leukemia not otherwise categorized. Two types of acute lymphoblastic leukemia are recognized based on immunologic characteristics: precursor B lymphoblastic leukemia/lymphoma and precursor T lymphoblastic leukemia/lymphoma. Precursor B acute lymphoblastic leukemia/lymphoma is subclassified into prognostic genetic groups. Biphenotypic leukemia is recognized as a form of acute leukemia of ambiguous lineage.
Topics: Acute Disease; Chromosome Aberrations; Humans; Immunophenotyping; Leukemia; World Health Organization
PubMed: 14552428
DOI: 10.1016/s0740-2570(03)00031-5 -
Nature Reviews. Cancer Feb 2021Although much work has focused on the elucidation of somatic alterations that drive the development of acute leukaemias and other haematopoietic diseases, it has become... (Review)
Review
Although much work has focused on the elucidation of somatic alterations that drive the development of acute leukaemias and other haematopoietic diseases, it has become increasingly recognized that germline mutations are common in many of these neoplasms. In this Review, we highlight the different genetic pathways impacted by germline mutations that can ultimately lead to the development of familial and sporadic haematological malignancies, including acute lymphoblastic leukaemia, acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Many of the genes disrupted by somatic mutations in these diseases (for example, TP53, RUNX1, IKZF1 and ETV6) are the same as those that harbour germline mutations in children and adolescents who develop these malignancies. Moreover, the presumption that familial leukaemias only present in childhood is no longer true, in large part due to the numerous studies demonstrating germline DDX41 mutations in adults with MDS and AML. Lastly, we highlight how different cooperating events can influence the ultimate phenotype in these different familial leukaemia syndromes.
Topics: Disease Progression; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Phenotype; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 33328584
DOI: 10.1038/s41568-020-00315-z -
British Journal of Haematology Jan 2020The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today,... (Review)
Review
The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today, state-of-the-art AML diagnostics relies on cytomorphology, cytochemistry, immunophenotyping, cytogenetics and molecular genetics. Only the integration of all of these methods allows for a comprehensive and complementary characterisation of each case, which is prerequisite for optimal AML diagnosis and management. Here, we will review why multidisciplinary diagnostics is mandatory today and will gain even more importance in the future, especially in the context of precision medicine. We will discuss ideas and strategies that are likely to shape and improve multidisciplinary diagnostics in AML and may even overcome some of today's gold standards. This includes recent technical advances that provide genome-wide molecular insights. The enormous amount of data obtained by these latter techniques represents a great challenge, but also a unique chance. We will reflect on how this increase in knowledge can be incorporated into the routine to pave the way for personalised medicine in AML.
Topics: Cytogenetic Analysis; Genome-Wide Association Study; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Precision Medicine
PubMed: 31808952
DOI: 10.1111/bjh.16360 -
British Journal of Haematology Jul 2018Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated... (Review)
Review
Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated transient abnormal myelopoiesis, which is not considered here, neonatal leukaemias are rare. In two-thirds of patients the disease manifests as an acute myeloid leukaemia, frequently with monocytic/monoblastic characteristics. Most other cases are acute lymphoblastic leukaemia, particularly B lineage, but some are mixed phenotype or blastic plasmacytoid dendritic cell neoplasms. The most frequently observed cytogenetic/molecular abnormality is t(4;11)(q21.3;q23.3)/KMT2A-AFF1 followed by t(1;22)(p13.3;q13.1)/RBM15-MKL1 and t(8;16)(p11.2;p13.3)/KAT6A-CREBBP. Common clinical features include prominent hepatosplenomegaly and a high incidence of skin involvement, sometimes in the absence of bone marrow disease. A distinctive feature is the occurrence of spontaneous remission in some cases, particularly in association with t(8;16). In this review, we summarise current knowledge of the clinical, cytogenetic and molecular features of neonatal leukaemia and discuss clinical management of these cases.
Topics: Antineoplastic Agents; Dendritic Cells; Diagnosis, Differential; Exanthema; Gene Order; Histone-Lysine N-Methyltransferase; Humans; Infant, Newborn; Leukemia; Myeloid-Lymphoid Leukemia Protein; Remission, Spontaneous; Treatment Outcome
PubMed: 29806701
DOI: 10.1111/bjh.15246 -
Annals of Hematology Apr 1992A small group of acute leukemias can be classified by morphological, cytochemical, or immunological marker analysis neither as acute lymphatic leukemia nor as acute... (Review)
Review
A small group of acute leukemias can be classified by morphological, cytochemical, or immunological marker analysis neither as acute lymphatic leukemia nor as acute myeloid leukemia. These leukemias are referred to as acute undifferentiated leukemia (AUL) and make up 2%-7% of the acute nonmyeloid leukemias. These leukemias are poorly defined in the literature and are also sometimes referred to as AML-MO. Most of the definitions include in the morphological and cytochemical criteria the expression of myeloid antigens. Here the value of these markers and of other techniques used in the diagnosis of undifferentiated or minimally differentiated leukemia is discussed. More than half of the leukemias that are undifferentiated by morphology and cytochemistry on the light-microscopic level show a positive reaction for myeloperoxidase by electron microscopy, which points to an early myeloid differentiation of those leukemias. Immunological marker analysis in most cases is inconclusive. Most show a positive reaction for CD 13, CD 33 or other myeloid-associated markers. However, in about half of these leukemias co-expression of lymphatic markers is seen. In a small minority, only lymphatic markers are expressed. Cytogenetic abnormalities which are found in these leukemias vary in type, and antigen receptor rearrangements are not lineage specific. Receptor studies, gene expression, and in vitro culture studies may, in the near future, contribute substantially to our knowledge about the commitment of these undifferentiated or minimally differentiated blasts. Recent definitions for AUL and AML-MO based on these different techniques are discussed.
Topics: Acute Disease; Humans; Leukemia; Leukemia, Myeloid; Microscopy, Electron
PubMed: 1581403
DOI: 10.1007/BF01696217 -
British Journal of Haematology Aug 1976A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases...
A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.
Topics: Acute Disease; Aged; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Cell Transformation, Neoplastic; Child; Esterases; Humans; International Cooperation; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Middle Aged; Peroxidase; Syndrome
PubMed: 188440
DOI: 10.1111/j.1365-2141.1976.tb03563.x -
Journal of Veterinary Diagnostic... Jul 2017Acute leukemia is rare in horses. Herein we describe historical, clinicopathologic, and postmortem findings in 6 horses with acute leukemia. Medical records of horses...
Acute leukemia is rare in horses. Herein we describe historical, clinicopathologic, and postmortem findings in 6 horses with acute leukemia. Medical records of horses with >20% bone marrow blasts and cytochemical or immunophenotyping results were reviewed. Affected horses were 2-8 y of age and of different breeds and sex. Horses were presented acutely with nonspecific signs (e.g., fever, lethargy). Characteristic hemogram findings were bi- or pancytopenia with low blast numbers. Histologic examination revealed extramedullary infiltrates, especially in lymph nodes, spleen, kidney, liver, and lungs. Leukemias were classified as B-cell ( n = 3) and acute myeloid leukemia (AML) ( n = 3). Tumors in 4 cases expressed multiple lineage markers, which complicated classification. Acute leukemia should be suspected in horses with moderate-to-severe bi- or pancytopenia. Blood smears should be reviewed for neoplastic cells, and bone marrow examination is required for diagnosis. Leukemia classification is best achieved using combined morphologic, cytochemical, and immunophenotyping results.
Topics: Animals; Biomarkers; Female; Horse Diseases; Horses; Leukemia, B-Cell; Leukemia, Myeloid, Acute; Male; New York
PubMed: 28467276
DOI: 10.1177/1040638717707724 -
Hematology/oncology Clinics of North... Dec 2011
Topics: Acute Disease; Humans; Leukemia
PubMed: 22093590
DOI: 10.1016/j.hoc.2011.10.003