Acute myeloid leukemia (AML) is a
malignancy of the bone marrow of which treatment strategies are still lacking efficacy. AML is characterized by the clonal expansion
and proliferation of aberrantly differentiated young cells (blasts) of the
myeloid cell line and is known for its clonal heterogeneity considering “morphology, cell
surface markers, genetic lesions, cell proliferation kinetics, and response to
therapy”i. (REFVAvd1 ). Clonal
expansion of these heterogenic cells causes a proliferation block of the
healthy precursor cells, resulting in failure of hematopoiesis of the myeloid
cell line and risk of anemia, acute bleeding and infectionii.
With current approaches, 70-80
percent of patients below the age of 60 achieve a morphologically assessedVAvd2 complete remission (CR) on protocol through remission-induction chemotherapy(1)(2)(REF)iii.
This remission induction therapy is
followed by post-remission consolidation treatment consisting of either
another round of chemotherapy, an allogenic stem cell transplant (allo-SCT) or
an autologous stem cell transplant (auto-SCT)(REF).
choice depends on the risk the individual has to relapse after achieving
complete remission as determined by the World Health Organization
(WHO) classification system (2008); dividing AML patients in a favorable, intermediate
and adverse risk groupiv.
this risk assessment has proven to be very useful at cohort level for risk
stratificationv40% of the patients initially
in CR experience disease recurrence, severely worsening their prognosis
Namely, this relapse is often much more difficult to treat than the initial
leukemia due to chemotherapy resistance and five-year survival rates of these
patients are low, varying from 35-40 percent (1)(REF). Because of these high
relapse rates, the search for predictors for early relapse risk assessment and
leukemia profiling has been an active field in leukemia research over the years
and many factors have proven to associate with either a poorer or a better
outcome in AML patients.
WHO risk-stratification already includes some of these factors and is mainly based on
cytogenetics and molecular abnormalities, characteristics that address this
previously discussed clonal heterogeneity of leukemic cells and are found in a
subset of patients.
The favorable risk group comprises of chromosomal rearrangements as well as
genetic mutations associated with good outcome amongst which karyotype
t(15;17) and inv(16t16)vii and mutations
CEBPA (bi-allelic) and NPM1. On the