Acute myeloid leukemia: the challenge of capturing disease variety.
The difference between success and failure of treatment of acute myeloid leukemia (AML) is largely determined by genotypic leukemia-specific differences among patients. The diversity of AML genotypes result from somatic genetic alterations settling down in succession in an individual's leukemia clone during the development of the disease. Gene mutations, gene expression abnormalities and other molecular alterations (e.g., microRNA variations) affect critical functions in AML cells, and may exert profound effects on the therapeutic response and outcome of the disease. Prototypes of common clinically significant gene aberrations involve transcription factors, signaling molecules and growth factor receptors. The expanding knowledge in this area allowing for risk stratified therapy decisions and the development of targeted drug therapy, is becoming an increasingly important part of the modern individualized clinical management of AML. This chapter highlights recent insights into the diagnostic, prognostic and therapeutic impact of chromosomal (e.g., the so-called monosomal karyotype) as well as particular genomic abnormalities, and presents examples of decision algorithms for individualized therapy.
Löwenberg
Bob
B
Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands. b.lowenberg@erasmusmc.nl
D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000074008:MDS1 and EVI1 Complex Locus Protein; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors