Gene Expression Profiling Yields Prognostic Information For AML Patients

NEW YORK (Reuters Health) - In patients with acute myeloid leukemia (AML), gene expression profiling identifies prognostic subclasses, according to two reports in The New England Journal of Medicine for April 15th. These findings are likely to lead to better risk stratification and treatment selection.

Even among patients with a normal karyotype, there appear to be two distinct subgroups with different outcomes, Dr. Jonathan R. Pollack, at Stanford University in California, told Reuters Health.

Until now, patients have been assigned treatment based primarily on cytogenetic factors, he explained. "But clinicians are not sure what to do with intermediate risk patients who have a normal karyotype."

"The gene expression signatures we identified may provide a basis for stratifying those patients," and thus determining the most appropriate candidates for the more risky but potentially more beneficial bone marrow transplant, he added.

Dr. Pollack and his colleagues determined the levels of gene expression in samples from 116 adults with AML, including 45 with a normal karyotype.

The two subclasses of patients with a normal karyotype were similar in age, gender, white-cell count, antecedent hematologic disorder and serum lactate dehydrogenase level.

In one of the groups, FLT3 aberrations and FAB morphologic subtype M1 or M2 were more common. In the second group, FAB subtype M4 or M5 were more common.

Survival outcomes were significantly different (p = 0.001), the report indicates. Thus, these two subtypes "appear to represent two different diseases, associated with distinct outcomes," Dr. Pollack said.

In the longer term, the gene signatures may "identify genes involved in pathogenesis, perhaps suggesting new treatment strategies," he added.

In the second report, investigators in the Netherlands led by Dr. Peter J. M. Valk, at Erasmus University Medical Center in Rotterdam, identified 16 gene expression clusters in 285 patients with AML, including five clusters that contained at least 20 patients each.

Three of these clusters had "a relatively favorable prognosis," the authors observe, with survival at 5 years ranging between 57% and 72%. There was a fourth cluster with intermediate survival (32% at 5 years). "Since these specimens were of the FAB M4 or M5 subtype, it is possible that genes related to monocytes or macrophages were important in the clustering of these cases," Dr. Valk's group proposes.

Because of an increased incidence of relapse in the fifth group, the prognosis was poor, with 18% survival at 5 years. The authors found these patients to be heterogeneous for poor-risk markers, so "the molecular signature of this cluster may signify a biochemical pathway that causes a poor outcome."

Even though different microarray platforms were used by the two research teams, "their results are surprisingly robust," Dr. Edison T. Liu and Krishna R. Karaturi, at the Genome Institute of Singapore, write in a Journal commentary.

And the strategy of gene expression profiling should yield "further insights in cases of AML with no known molecular markers," Dr. David Grimwade, at University College London, and Dr. Torsten Haferlach, at University Hospital Grosshadern in Munich, Germany, predict in a related editorial.

Source: N Engl J Med 2004;350:1595-1597,1605-1628,1676-1678. [ Google search on this article ]

MeSH Headings: Genetic Techniques : Human Activities : Investigative Techniques : Survival : Gene Expression Profiling : Analytical, Diagnostic and Therapeutic Techniques and Equipment : Anthropology, Education, Sociology and Social Phenomena