This review summarizes the reported molecular mechanisms underlying the antileukemic property of
Sesquiterpene Lactones (SLs). This systematic review was registered in the PROSPERO database and conducted
following the PRISMA Statements. The MeSH terms, Sesquiterpenes, Lactones and Leukemia were used
in four databases (Pubmed, Web of Science, Scopus and Bireme). There were 281 studies selected, but after
exclusions, due to replication (n = 172) or not following PECOS criteria (n = 24), 148 studies remained. Of the
148 articles, only 22 were submitted to quality assessment and were scored in high level if more than two techniques,
to elucidate antileukemic properties, were described, and then data were extracted. The studies mostly
used human leukemia cell lines including primary and established cells, with or without chemotherapy resistance.
The SLs used were obtained principally from plants. The antileukemic properties of SLs were extracted
from 22 high level studies. They included cell death induction, mainly by apoptosis, as well as cell differentiation,
cell cycle disruption, leukemia cancer stem cell growth inhibition and NF-κB pathway inhibition; the latter
is a promising therapeutic target for lymphoid malignancies. We concluded that, in spite of the necessity of
better toxicological profile characterization of SLs, the antileukemic properties of these compounds support the
proposal that the SLs are promising candidates for the treatment of leukemia.