Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances.
OBJECTIVE
Molecular study of cytogenetically normal acute myeloid leukemia is among the most active areas of leukemia research. Despite having the same normal karyotype, adults with de-novo cytogenetically normal acute myeloid leukemia who constitute the largest cytogenetic group of acute myeloid leukemia, are very diverse with respect to acquired gene mutations and gene expression changes. These genetic alterations affect clinical outcome and may assist in selection of proper treatment. Herein we critically summarize recent clinically relevant molecular genetic studies of cytogenetically normal acute myeloid leukemia.


RESULTS
NPM1 gene mutations causing aberrant cytoplasmic localization of nucleophosmin have been demonstrated to be the most frequent submicroscopic alterations in cytogenetically normal acute myeloid leukemia and to confer improved prognosis, especially in patients without a concomitant FLT3 gene internal tandem duplication. Overexpressed BAALC, ERG and MN1 genes and expression of breast cancer resistance protein have been shown to confer poor prognosis. A gene-expression signature previously suggested to separate cytogenetically normal acute myeloid leukemia patients into prognostic subgroups has been validated on a different microarray platform, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are still needed.


CONCLUSIONS
The discovery of new prognostic markers has increased our understanding of leukemogenesis and may lead to improved prognostication and generation of novel risk-adapted therapies.
Mrózek
Krzysztof
K
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive, Cancer Center, The Ohio State University, Columbus, Ohio 43210-1228, USA. krzysztof.mrozek@osumc.edu
Döhner
Hartmut
H
Bloomfield
Clara D
CD
D000208:Acute Disease; D015415:Biomarkers / Q000032:analysis; D052138:Genes, Neoplasm; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis
D015415:Biomarkers; C000716967:NPM1 protein, human; D000090243:Nucleophosmin