New insights into the biology of acute myeloid leukemia and their impact on treatment.
Acute myeloid leukemia (AML) is a heterogeneous group of disorders that can be discriminated by morphology, immunophenotyping or more recently by cytogenetic and molecular techniques. By cytogenetics two major groups of AML can be discriminated: One group with detectable chromosomal aberrations accounting for approximately 52 % of all de novo AML and the second group without cytogenetically detectable karyotype abnormalities. In the first group two major subtypes can be further distinguished. The first group comprises AML with balanced aberrations mainly consisting in t(8;21), t(15;17) and inv(16). The second group comprizes cases with unbalanced aberrations including particularly 5q-, 17q- -5 and AML with complex karyotypes. AMLs with balanced aberrations have a good prognosis with long term survival being achieved in approximately 60 %-80 % of cases. AMLs with non-balanced aberrations on the other hand have a poor prognosis with only 10 %-15 % long-term survivors. AMLs with no detectable abnormalities or other cytogenetic aberrations comprise a group with an intermediate prognosis in which long term survival is achieved in approximately 25 %-30 % of cases. Biologically, AMLs with balanced aberrations regularly involve the deregulation of transcription factors resulting in an impairment of cell differentiation and proliferation. AMLs with unbalanced aberrations are mostly characterized by a loss of genetic material resulting in an alteration of cell cycle control and DNA repair. A new view on the biology of AML has recently been made possible through the analysis of gene expression profiles. This technique is still under investigation. First results, however, already show that gene expression patterns have a high diagnostic potential and allow to detect biology subgroups with a high accuracy. Furthermore, by this technique pathways can be identified that are altered in the leukemic process. Gene expression profiling therefore opens a new and exciting perspective in leukemia biology and therapy that may have substantial impact on the improvement of diagnosis and more importantly may guide therapeutic strategies.
Hiddemann
W
W
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University Munich.
Haferlach
T
T
Schoch
C
C
Behre
G
G
Kohlmann
A
A
Kern
W
W
Feuring-Buske
M
M
Bohlander
S
S
D000208:Acute Disease; D017668:Age of Onset; D002869:Chromosome Aberrations; D020869:Gene Expression Profiling; D006801:Humans; D015994:Incidence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics / Q000473:pathology* / Q000628:therapy