Gene Clustering Helps to Classify Patients with AML

Gene Clustering Helps to Classify Patients with AML

According to two recent publications in The New England Journal of Medicine, expressions of specific clusters of genes help to classify patients with acute myeloid leukemia, ultimately leading to more individualized treatment options.

Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the uncontrolled growth of immature white blood cells (immune cells), which never develop into functioning cells. Besides not being able to carry out the functions of mature immune cells, AML cells may also crowd out normal blood cells in the bone marrow and blood. AML is considered to be an aggressive cancer and patients are often at a high risk of developing a cancer recurrence following therapy, particularly if they are not able to undergo high doses of therapy. Chromosomal variables of AML cells, as well as levels of cancer cells in the blood, prior hematologic disorders and levels of specific enzymes may help to further distinguish patients into being at a high-risk, standard-risk or low-risk of developing a cancer recurrence, and treatment may be altered according to these stratifications. However, it is estimated that only approximately 50% of patients may be accurately classified into appropriate risk stratifications and further refinement in classifications are needed.

The expression of various combinations of genes, called gene expression profiling, is rapidly being recognized as an important tool in determining disease characteristics, and ultimately providing a platform to create individual treatment regimens. Researchers are learning that within one type of cancer, different gene profiles aid in predicting the risk of a cancer recurrence and/or the response potential to specific therapies.

The first clinical trial evaluating gene expression profiling in AML was conducted by researchers from the Netherlands. This study included 285 patients who had already been classified into risk stratification groups according to standard methods. The patients then had samples of genetic material analyzed through laboratory processes to detect specific gene expression clusters that were associated with outcomes in these patients. The researchers found 3 distinct groups with certain clustering patterns that were associated with good, intermediate and poor survival long-term outcomes. The group with the highest survival probability according to gene expression profiling had an approximate 72%-57% rate of survival at 60 months, compared with an approximate 32% rate of survival in the intermediate survival group and an 18% rate of survival in the poor survival group. The variances of survival within the high-survival group were associated with differences in the overall clustering within the group, with 3 distinct clusters distinguished within the group.

The second clinical trial evaluating gene expression profiling in AML was conducted by researchers from Stanford University. This study included samples from the blood or bone marrow of 116 patients with AML. Forty-five of these patients had intermediate-risk normal karyotype (arrangement of chromosomes) AML, a classification of AML for which no consensual risk stratification exists at present. Therefore, refinement in classification for intermediate-risk, normal karyotype AML is of particular importance in order to provide the most appropriate treatment for these patients. Following gene expression profiling of all of the patients, researchers were able to detect associations between specific gene clusters and survival. Particularly, patients with a normal karyotype AML were divided into two groups according to specific gene expression profiling – one group with significantly higher survival than the other group.

The researchers from both trials concluded that gene expression profiling may help to classify patients with AML, even those with a normal karyotype, ultimately leading to a more individualized treatment approach to improve chances of optimal long-term survival. Future clinical studies evaluating gene expression profiling is warranted for patients with AML. Patients diagnosed with AML may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating gene expression profiling or other novel approaches to risk stratification. Two sources of information regarding ongoing clinical trials include the National Cancer Institute ( cancer.gov) and www.cancerconsultants.com. Personalized clinical trial searches are also performed on behalf of cancerconsultants.com.

Reference: Valk P, Verhaak R, Beijen M, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. The New England Journal of Medicine. 2004;350:1617-1628.

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