Type: Research Essays
Sample donated: Annie Buchanan
Last updated: August 22, 2019
Acute myeloid leukemia (AML) is amalignancy of the bone marrow of which treatment strategies are still lacking efficacy. AML is characterized by the clonal expansionand proliferation of aberrantly differentiated young cells (blasts) of themyeloid cell line and is known for its clonal heterogeneity considering “morphology, cellsurface markers, genetic lesions, cell proliferation kinetics, and response totherapy”i. (REFVAvd1 ). Clonalexpansion of these heterogenic cells causes a proliferation block of thehealthy precursor cells, resulting in failure of hematopoiesis of the myeloidcell line and risk of anemia, acute bleeding and infectionii.
With current approaches, 70-80percent 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 eitheranother round of chemotherapy, an allogenic stem cell transplant (allo-SCT) oran autologous stem cell transplant (auto-SCT)(REF). Treatmentchoice depends on the risk the individual has to relapse after achievingcomplete remission as determined by the World Health Organization(WHO) classification system (2008); dividing AML patients in a favorable, intermediateand adverse risk groupiv.
Althoughthis risk assessment has proven to be very useful at cohort level for riskstratificationv40% of the patients initiallyin CR experience disease recurrence, severely worsening their prognosisthereafter(1)vi.Namely, this relapse is often much more difficult to treat than the initialleukemia due to chemotherapy resistance and five-year survival rates of thesepatients are low, varying from 35-40 percent (1)(REF). Because of these highrelapse rates, the search for predictors for early relapse risk assessment andleukemia profiling has been an active field in leukemia research over the yearsand many factors have proven to associate with either a poorer or a betteroutcome in AML patients. ThisWHO risk-stratification already includes some of these factors and is mainly based oncytogenetics and molecular abnormalities, characteristics that address thispreviously discussed clonal heterogeneity of leukemic cells and are found in asubset of patients.The favorable risk group comprises of chromosomal rearrangements as well asgenetic mutations associated with good outcome amongst which karyotypeaberrancies t(8;21),t(15;17) and inv(16t16)vii and mutationsCEBPA (bi-allelic) and NPM1. On the