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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute promyelocytic leukaemia (APL) with M3 (or M3v) morphology is the only AML subtype to date for which morphology and immunophenotype agree. In other words, FAB M3 is interchangeable with a unique marker profile. More precisely, we have finally recognized a surrogate marker profile for leukaemia derived from the (15;17) translocation and expressing PML/RARalpha transcripts. To present this as a new development may come as a surprise to many. After all, the antigen expression pattern of AML-M3 was well recognized for many years: absence or weak expression of HLA-DR, CD117, CD15, CD11b and CD34 in the context of a myeloid phenotype (CD33 and CD13 expression) and frequently associated with moderate to high side-scatter appearance upon flow cytometric evaluation, depending upon the degree of granularity of the leukaemic cells. While partially correct, this established APL phenotype is both flawed and limited in its ability to distinguish APL from other AML subtypes, such as natural-killer-cell AML. Given the availability of phenotype-specific therapy for APL, such as all-trans retinoic acid or arsenic trioxide, failing to diagnose APL or misdiagnosing a case of AML with an APL-like phenotype will result in serious clinical consequences. Faced with this dilemma, we have recently performed a comprehensive immunophenotypic analysis of APL patients entered on Eastern Cooperative Oncology Group trials. Our results give diagnostic power to only three antigens, HLA-DR, CD11a and CD18, all of which are characteristically expressed at low levels by APL cells. Despite some significant antigenic differences (e.g. in CD34 expression), this surrogate marker profile for t(15;17) APL applies to both the M3 and the M3v FAB phenotypes and to all three isoforms of the PML/RARalpha transcript.
Best Pract Res Clin Haematol 2003 Sep
PMID:Expression of cell-surface antigens in acute promyelocytic leukaemia. 1293 57

Our understanding of the genetic basis of acute myeloid leukaemias has been enhanced through cloning of recurring chromosomal translocation breakpoints. However, the remarkable observation, more than a decade ago, that all-trans retinoic acid (ATRA) induced remission in patients with t(15;17) acute promyelocytic leukaemia (APL) was a driving force in the subsequent cloning and characterization of the PML-RARalpha fusion that is causally implicated in the pathogenesis of this disease. Major improvements in treatment and outcome of APL patients have been made since that time by incorporating ATRA in conventional chemotherapy but 30% of APL patients still succumb to complications of their disease or their therapy. Recent information that the haematopoietic receptor tyrosine kinase FLT3 is mutated in about 30% of APL patients suggests strategies for further improving treatment and outcome in this subset of APL patients using small-molecule inhibitors of FLT3. The role of FLT3 mutations in APL and other AML will be discussed.
Best Pract Res Clin Haematol 2003 Sep
PMID:FLT3-activating mutations in acute promyelocytic leukaemia: a rationale for risk-adapted therapy with FLT3 inhibitors. 1293 59

Acute promyelocytic leukaemia (APL), designated M3, is a particularly interesting subtype of acute myeloid leukaemia (AML) that has unique molecular and clinical characteristics. It is characterized by an arrest of myeloid differentiation at the promyelocyte stage with abnormal proliferation of these cells. Recent paediatric and adult trials which included all-trans retinoic acid (ATRA) have shown that APL has significantly better survival rates than other subtypes of AML. While there is extensive literature on APL in adults, articles dedicated to describing solely paediatric patients are limited. This chapter focuses on the incidence, diagnosis, clinical characteristics, treatment, and survival rates of children with APL.
Best Pract Res Clin Haematol 2003 Sep
PMID:Acute promyelocytic leukaemia in children. 1293 64

Acute promyelocytic leukaemia (APL) may be characterized simultaneously as the most potentially rapidly fatal human acute leukaemia if untreated, yet the most frequently cured acute leukaemia if promptly diagnosed and treated without delay. Co-operative group and single-institution studies which include large numbers of patients with relatively long follow-up demonstrate that, with all-trans retinoic acid (ATRA) plus anthracycline-based chemotherapy, the majority of newly-diagnosed patients appear cured of their disease. The 5-year disease-free survival rates range from 75 to 85%. Early death is still observed in approximately 10% of patients and remains a difficult obstacle to increasing the cure rate. Prognostic factors which identify patients at high risk for recurrence are becoming increasingly recognized. Older age (over age 55-60 years), elevated white blood cell count at presentation (higher than 5,000-10,000/microl), and expression of CD56 unfavourably influence outcome. The treatment of such patients remains a challenge, although it is important to note that APL is the only type of AML in which a significant proportion of older patients may be cured. Because more patients are cured of their disease, potential long-term consequences may become increasingly recognized. These include the emergence of extramedullary disease, the development of secondary myelodysplasia or acute myeloid leukaemia and the potential for late-onset cardiac toxicity.
Best Pract Res Clin Haematol 2003 Sep
PMID:Long-term follow-up and potential for cure in acute promyelocytic leukaemia. 1293 68

In patients with acute leukaemia, studies of minimal residual disease (MRD) provide powerful and independent prognostic information. Multiparameter flow cytometry is a widely applicable and reliable approach for monitoring MRD. Using triple or quadruple marker combinations, aberrant or uncommon phenotypic profiles can be identified in about 80% of patients with acute myeloid leukaemia (AML) and 95% of patients with acute lymphoblastic leukaemia (ALL). These profiles can reveal leukaemic cells even when these are not evident by morphological analysis. Thus, one leukaemic cell among 1000-10000 normal bone marrow or peripheral blood cells can be routinely detected. In this chapter we discuss technical aspects of MRD detection by flow cytometry and summarize results of correlative studies between MRD, clinical and biological features of leukaemia and treatment outcome. Current knowledge indicates that MRD studies using well-tested methodologies are clinically useful and should be incorporated into the clinical management of patients with acute leukaemia.
Best Pract Res Clin Haematol 2003 Dec
PMID:Minimal residual disease monitoring by flow cytometry. 1459 45

Numerous immunophenotypic features have been examined for their potential prognostic significance in predicting treatment outcome in leukaemias. These include immunophenotypic subgroups of acute lymphoblastic leukaemia (ALL) and immature acute myeloid leukaemia, expression of individual surface antigens or combined immunophenotypic features, and more recently, molecules mediating the multidrug resistance phenotype or being involved in the regulation of drug-induced apoptosis. Most previous studies investigating the prognostic significance of antigen expression in leukaemia have not used the information provided by multiparameter flow cytometry and have chosen rather arbitrary cut-off points for marker positivity. Moreover, given significant associations between immunophenotypic features and genetic abnormalities in leukaemic cells, immunophenotyping as an independent predictor of treatment outcome has been questioned. Thus, except for lineage assignment of leukaemic blasts and definition of maturational status in ALL, information provided by immunophenotyping is currently not applied to risk-classification systems or used for planning patient treatment in leukaemia. We review some of the recent findings regarding the prognostic impact of distinct immunophenotypic features in acute leukaemias and myelodysplastic syndrome.
Best Pract Res Clin Haematol 2003 Dec
PMID:The prognostic significance of antigen expression in leukaemia. 1459 46

Immunophenotyping of acute and chronic leukaemias has revealed many lineage- and differentiation-specific antigens. It has now become possible to classify leukaemias according to their unique antigenic expression pattern. Among many lineage- and differentiation-specific antigens, disease-specific antigens are increasingly recognized because of their specific prognostic or therapeutic relevance. Expression of the multidrug resistance proteins of the ABC transporter family is associated with a poor response to treatment and a grave clinical prognosis. Recently, attempts to reverse refractory disease by using P-glycoprotein inhibitors have been performed in acute myeloid leukaemia, so far without evidence of clinical benefit. Other new leads to use antigen expression as a way of designing tumour-specific therapy have resulted in imatinib and Flt3 inhibitors which target tyrosine kinases in the leukaemic cell. Clinical trials are underway to investigate the effect of these new agents. The development of an antibody-calicheamycin complex directed against the myeloid-specific antigen CD33 has shown clinical activity in patients with relapsed acute myeloid leukaemia. The further development of these approaches is discussed.
Best Pract Res Clin Haematol 2003 Dec
PMID:Immunophenotyping as a guide for targeted therapy. 1459 47

Recent advances in molecular genetics have advanced the knowledge regarding the mechanisms leading to myelodysplastic syndrome (MDS), secondary acute myeloid leukemia, and therapy-induced MDS. Unfavorable cytogenetics associated with this group of disorders includes monosomy or deletion of the long arm of chromosomes 5 or 7, inversions of chromosome 3, translocations, deletions, and trisomies involving several other chromosomes. These unbalanced chromosomal aberrations result in hemizygosity and unmasking of oncogenes, changes in levels of expressed genes, or inactivation of tumor suppressor genes. It is evident that the cytogenetics associated with MDS is highly complex and heterogeneous, leading to an equally heterogeneous manifestation of the disease. Classifications, initially defined by the French-British-American group followed by the World Health Organization, and now by the International Prognostic Scoring System, have determined prognosis and helped develop treatment strategies for these patients, thus reducing their potential to develop acute leukemia. To date there are seven different prognostic schemas. These are constantly being improved so that MDS patients, who tend to be elderly, can be suitably treated. Additionally, treatment considerations and prognosis are different for patients who develop therapy-related MDS or for the juvenile population than for those with de novo MDS. The genetic alterations in MDS bone marrow and blood cells have been identified and possible models have been proposed for the development and progress of MDS, from the early stage to late-stage MDS evolving to acute myeloid leukaemia. As the functional mechanisms behind these chromosomal changes are being revealed, new therapies based on these mechanisms are currently being made and tested.
Best Pract Res Clin Haematol 2004 Dec
PMID:Pathobiology, classification, and diagnosis of myelodysplastic syndrome. 1549 93

Myelodysplastic syndrome (MDS) is an acquired bone marrow disorder characterized by ineffective hematopoiesis and cellular dysfunction and has an increased risk of transforming into acute myeloid leukemia. Most patients are of advanced age with attendant comorbidities, making treatment difficult. Current treatment options have included supportive care and, in difficult cases, chemotherapy regimens designed for acute leukemia patients. A major effort has been made to determine the role of stem cell transplantation in adult MDS patients, currently the only curative option available for them. Based on relapse rates, studies indicate that allogeneic and autologous transplants provide better antileukemic activity than intensive chemotherapy schedules. Use of DNA methyltransferase inhibitors may assist in managing MDS patients while awaiting a transplant match, but the procedural mortality for transplant remains high. Reduced conditioning or nonmyeloablative conditioning, particularly in the elderly, has been attempted with some success. Reduced conditioning also increases the graft-versus-leukemia effect, allowing for a higher percentage of disease-free survival. Current use of peripheral blood as a source of stem cells for autotransplant is associated with an extremely low procedural mortality. Improvement in such transplant procedures as myeloablation, preparation of the autograft, and posttransplant prophylaxis are improving recovery rates for these patients. In addition, as the biology of this disease is being revealed, newer options will become available in the near future.
Best Pract Res Clin Haematol 2004 Dec
PMID:Transplant strategies for myelodysplastic syndrome. 1549 94

Treatment of myelodysplastic syndrome (MDS) has been hampered by the lack of understanding of the molecular and biological abnormalities associated with this disease. Biological abnormalities may lead to typical phenotypic changes in more differentiated cells. Recent developments in the natural history and underlying molecular mechanisms of MDS and acute myeloid leukemia (AML) have identified new molecular therapeutic targets. Several new classes of drugs have shown promise in early clinical trials and may alter the standard of care of these patients. Among these new drugs are farnesyltransferase inhibitors, receptor tyrosine kinase inhibitors, protein kinase C inhibitors, and VEGF inhibitors. These agents have been tested in patients with solid tumors and hematological malignancies such as AML and MDS. Most of the studies in MDS are in early stages of development, where doses are being determined based on the experience in refractory or relapsed AML or solid tumors. Future therapies in MDS will attempt to resolve cytopenias, eliminate malignant clones and allow differentiation by attacking specific mechanisms of the disease.
Best Pract Res Clin Haematol 2004 Dec
PMID:Inhibitors of signaling in myelodysplastic syndrome. 1549 98


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