High cytogenetic or molecular genetic risk acute myeloid leukemia.
Resistance, manifested as failure to enter remission despite living long enough to do so or as relapse from remission, is the principal cause of therapeutic failure in acute myeloid leukemia, even in patients age ≥ 75. Recently, a "monosomal karyotype" in acute myeloid leukemia blasts has been found to be a principal predictor of resistance. It is also clear that patients with a normal karyotype, and other intermediate prognosis karyotypes, can be placed into a high-risk group based on the absence of a mutation in the NPM1 gene or the presence of an internal tandem duplication (ITD) of the Fms-like tyrosine kinase 3 gene (FLT3) gene, particularly if there is loss of the wild-type FLT3 allele. The effects of other genetic abnormalities have been inconsistent, perhaps reflecting differences in expression of the abnormality and its translation into protein. Several reports have shown the prognostic potential of profiling global gene expression, micro-RNA expression, DNA methylation, and proteomics. Although routine application of these approaches is still premature, pretreatment assessment of the nucleophosmin 1 (NPM1) mutation and FLT3 ITD status, as well as cytogenetics, should be routine. These results can be used to guide the choice of remission induction therapy, for example, by placing patients with monosomal karyotype or FLT3 ITDs on clinical trials. Allogeneic hematopoietic cell transplant in first complete remission is generally indicated for high-risk patients. However, new approaches are needed to reduce the high rates of relapse, even after hematopoietic cell transplant.
Division of Hematology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. eestey@uw.edu
Elihu
E
Estey
D000970:Antineoplastic Agents / Q000627:therapeutic use; D020732:Cytogenetic Analysis; D020440:Gene Duplication / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D000090243:Nucleophosmin; D012307:Risk Factors
D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D000090243:Nucleophosmin