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Application Of Microarrays In Diagnosis, Treatment And Prognosis Of Acute Myeloid Leukemia

1923 words - 8 pages

Introduction
Acute Myeloid Leukemia (AML) is a heterogeneous disease characterized by clonal malignant hematopoiesis with a differentiation arrest and excessive proliferation of leukemic blasts.6 It is one of the most common types of leukemia among adults. This type of cancer is rare under age 40. The median age of patients with AML is 63 years.2 Clinically, patients present with fever, fatigue, and spontaneous mucosal and cutaneous bleeding, due to abnormalities in red blood cells.1 Opportunistic infections are also common, due to the lack of normal white blood cells.1 Most patients with AML achieve complete remission after chemotherapy and/or stem cell transplantation (SCT). 2 ...view middle of the document...

3 Among CN-AML, CEBPA mutations have been associated with a favorable outcome.3 FLT3 is a member of the class III receptor tyrosine kinase family.3 FLT3 and its ligand play an important role in proliferation, survival, and differentiation of hematopoietic progenitor cells. 3 FLT3 mutations are not a distinct entity, they often occur with other mutations and provide important prognostic information.3 NPM1 mutation without concurrent FLT3 internal tandem duplication (ITD) predicts favorable outcome. Prognosis of CN-AML with FLT3-ITD is significantly inferior.3 All other gene mutations identified in AML have not yet entered clinical practice and remain investigational. (i.e. ITD, TKD, IDH1, IDH2, KIT, etc).3 In addition to mutations, a number of downregulated genes have been identified in AML as well. (i.e. BAALC,ERG,EVI1,MN1).3

Given such a large number of mutations found in AML, which lead to complexity of this disease, and what I recently learned in Genomics and Proteomics class about microarray analysis, I was interested in researching more about microarray technology and its utilization in diagnosis and treatment of this disease.

Microarrays as a Tool to Identify Novel Genes involved in AML
Microarray is an assay that screens for presence and expression of genes in a sample. The microarray technology is now widely recognized and has become an important tool in diagnostics, including personalized medicine. I found numerous research articles, which demonstrate utilization of microarray analysis to further understand gene expression changes in AML and its application to the diagnosis and prognosis of AML. However, at this time, in the USA, gene expression profiling in AML is being utilized only within the research setting. Many studies are underway that investigate identification of novel genes. One example of this is study done by Parkin and colleagues. They used a chromosomal microarray analysis, array based comparative genomic hybridization (aCGH), which can detect structural variations. By using this technique they were able to identify a novel gene NF1 that has a pathological significance in AML. They found a loss of functional NF1 gene in 7% of AML patients.5

Microarrays and identifying distinct sub-groups in AML
DNA microarray analysis has the potential to identify distinct sub-groups of AML with the use of one comprehensive assay, to classify cases that currently resist categorization by means of other methods, and to identify subgroups with favorable or unfavorable prognoses.8 Valk and colleagues used microarray technology to determine gene expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML. They identified 16 groups of patients with AML on the basis of molecular signatures. They clustered the genes on the basis of the presence of chromosomal lesions (e.g., t(8:21), t(15:17) and inv(16), genetic mutations (CEBPA), and abnormal oncogene expression. Several novel...

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