Prognostically Important Molecular Markers in Cytogenetically Normal Acute Myeloid Leukemia
Section of Hematology and Oncology, Department of Internal Medicine, Stanley S. Scott Cancer Center, LSU Health Sciences Center-New Orleans, New Orleans, Louisiana 70112, USA. The American Journal of the Medical Sciences
(Impact Factor: 1.39).
05/2011; 341(5):404-8. DOI: 10.1097/MAJ.0b013e318201109d
Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with variable clinical outcomes. Emerging data has identified molecular markers that provide additional prognostic information to better classify these patients into those with a more favorable prognosis and those with an unfavorable prognosis who may require more aggressive or investigational therapies. Markers such as mutations in nucleophosmin 1 gene and CCAAT/enhancer binding protein alpha gene have been associated with a more favorable prognosis in CN-AML. In contrast, FMS-related tyrosine kinase 3 mutations, partial tandem duplication of mixed-lineage leukemia gene and overexpression of brain and acute leukemia, cytoplasmic gene are associated with inferior clinical outcomes. In this article, the authors discuss the classical clinical features of AML and the importance of cytogenetics that predict prognosis in AML. They review the best-described molecular markers in CN-AML and their significance to clinical decision making in CN-AML.
Available from: Timothy Chevassut
- "However, there is variation between different cooperative groups as to the correct stratification of different mutations . Furthermore, nearly half of the patients have cytogenetically normal (CN) AML and are ascribed to the intermediate risk category despite significant heterogeneity . It is clear, therefore, that molecular mutational analysis has "
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ABSTRACT: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.
Advances in Hematology 03/2014; 2014(8):103175. DOI:10.1155/2014/103175
Available from: Carlos Martínez Murillo
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ABSTRACT: to compare the frequency of acute leukemia in two periods of study in a reference Hospital at Mexico City.
it was an observational study. There were registered 250 cases with the morphology diagnostic criterion of acute leukemia.
63 cases versus 92 of acute lymphoid leukemia (ALL) and 16 versus 79 acute myeloid leukemia (AML) of 1990-1992 versus 2008-2009 respectively was observed; corresponding to 62 % in total of ALL in both periods and 38 % of AML. The ALL was the most frequent variant (62 % versus 38 %). The median age was 26 years, male 52 %. It showed a significant increase in the number of admissions in the period of 2008-2009 and acute promyelocytic leukemia also showed an increase (p = 0.001).
acute leukemia is the main cause of admission, mortality and morbidity. Our study differs slightly from the literature; the leukemia that diagnostic with major frequency was the acute lymphoid leukemia increasing his number in the period of 2008-2009. The significant rise due to an increase use of new diagnostic tools such as the flow cytometry and molecular biology.
Revista medica del Instituto Mexicano del Seguro Social 03/2012; 50(2):167-71.
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ABSTRACT: Abstract Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of Wnt/β-catenin signaling pathway and its dysregulation is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF1 in acute myeloid leukemia (AML) and determined its specific prognostic significance in this disease. LEF1 mRNA level in patients with previously untreated AML was significantly higher than normal controls. AML patients with relatively higher LEF1 expression were more likely to achieve CR following induction therapy in comparison to those with lower LEF1 level. Moreover, we provide the first evidence that primary AML samples with AML1-ETO or PML-RARα have higher LEF1 level compared with those without each fusion gene. High LEF1 expression predicts a significantly better overall survival for patients with intermediate-risk cytogenetics. High LEF1 level was associated with a favorable relapse free survival in patients with FLT3-ITD wild-type. Finally, a scoring system based on LEF1 level and mutation status of FLT3-ITD or NPM1 is reliable to predict the outcome for AML with intermediate-risk cytogenetics. Our results indicate that LEF1 contributes to the pathophysiology of AML and could serve as a novel predictor of better treatment response. LEF1 level may be incorporated in an improved risk classification system for certain specific subtype of AML.
Leukemia & lymphoma 05/2013; 55(2). DOI:10.3109/10428194.2013.805759 · 2.89 Impact Factor
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