Page 74 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Molecular shift in FLT3 during AML course

“Leukemia*, Acute Myeloid” OR “Leukemia, Myeloblastic, were read to ensure eligibility. Subsequently, the reference
Acute” OR “Leukemia, Myelocytic, Acute” OR “Leukemia, lists of each included article were reviewed to identify any
Myelogenous, Acute” OR “Leukemia, Nonlymphoblastic, additional studies that may have been missed during the
Acute” OR “Leukemia, Nonlymphocytic, Acute” OR database search.
“Myeloblastic Leukemia*, Acute” OR “Acute Myeloblastic Data were collected from retrospective, prospective,
Leukemia*” OR “Leukemia*, Acute Myeloblastic” OR or interventional studies involving patients with relapsed/
“Myelocytic Leukemia*, Acute” OR “Acute Myelocytic refractory AML. Extracted data included study design,
Leukemia*” OR “Leukemia*, Acute Myelocytic” OR year of publication, number of patients, FLT3 mutational
“Myelogenous Leukemia, Acute” OR “Myeloid Leukemia*,
Acute” OR “Nonlymphoblastic Leukemia*, Acute” OR status at diagnosis and relapse using paired samples, type
“Acute Nonlymphoblastic Leukemia*” OR “Leukemia*, of FLT3 mutation (ITD, TKD, or wild-type), as well as
Acute Nonlymphoblastic” OR “Nonlymphocytic karyotype, French–American–British (FAB) classification,
Leukemia*, Acute” OR “Acute Nonlymphocytic and allelic burden. FLT3 mutational status was considered
Leukemia*” OR “Leukemia*, Acute Nonlymphocytic” OR to have changed if paired samples from the same patient
“Acute Myelogenous Leukemia*” OR “Leukemias, Acute displayed different results at diagnosis and the relapse/
Myelogenous” OR “Myelogenous Leukemias, Acute” refractory stage. The study’s article inclusion flowchart,
OR “Myeloid Leukemia, Acute, M1” OR “Leukemia, based on PRISMA methodology, is presented in Figure 1.
Myeloid, Acute, M1” OR “Acute Myeloid Leukemia 3. Results
without Maturation” OR “Leukemia, Myeloid, Acute, M2”
OR “Myeloid Leukemia, Acute, M2” OR “Acute Myeloid Following the initial search conducted in 2020, 1,201
Leukemia with Maturation*” AND “Recurrence”[MeSH articles were identified. After screening the titles and
terms] OR “Recrudescence” OR “Recrudescences” OR abstracts, 513 were selected for further analysis. Of these,
“Recurrences” OR “Relapse” OR “Relapses.” after evaluation of the methodology and results, 12 articles

No date restriction was applied. An updated search was were eligible for full-text review, and an additional five
conducted in July 2024 to include newly published articles. were retrieved through manual reference list searches.
After the initial screening of titles and abstracts, eligible Among the full-texts reviewed, five were excluded due to
articles were selected for full-text review. No articles were a lack of relevant data on FLT3 mutational status, and one
excluded due to sample size. No particular subgroup of due to divergent population selection criteria.
AML was selected for analysis. In the updated 2024 search, 1,641 articles were
retrieved. After screening, 161 were selected based on titles
2.2. Inclusion and exclusion criteria and abstracts. Of these, 56 underwent full-text analysis; 19
Studies were included if they: (i) investigated adult studies were excluded for not using PCR as the detection
patients with AML; (ii) were written in English, Spanish, method, 10 overlapped with the initial search, and 16
or Portuguese; (iii) employed PCR as the method for did not report paired sample data or detailed mutational
detecting FLT3 mutations, as it is considered the current profiles. In addition, two were excluded for comparing
gold standard; and (iv) reported FLT3 mutational status different PCR techniques, and nine were ultimately
at both diagnosis and relapse/refractory stages. The included. In total, 20 studies met the inclusion criteria
exclusion criteria were: (i) studies exclusively involving (Figure 1).
pediatric populations, (ii) studies focusing solely on acute All included studies employed PCR as the method for
promyelocytic leukemia; (iii) phase I interventional clinical FLT3 mutational analysis; 11 studies assessed both FLT3-
trials; (iv) preclinical studies; (v) review articles, letters to
the editor, and case reports; and (vi) studies lacking data ITD and FLT3-TKD, eight assessed only FLT3-ITD, and
on paired samples or failing to report FLT3 mutational one focused exclusively on FLT3-TKD (Table 1). The year
status at both relevant time points. of publication of the works selected in this study ranged
from 1999 to 2014. Only three studies were prospective;
2.3. Study selection and data extraction the others were retrospective. Just one study that evaluated
both FLT3-ITD and FLT3-TKD indicated robust
Articles were screened by one of the authors (L.T.). The
selection process involved reviewing the title and abstract, longitudinal data with paired samples.
followed by a methodological analysis of each study to The quality of the studies varied substantially. Only one-
identify the technique used for mutation analysis (PCR third of publications had samples larger than 100 patients.
vs. NGS) and whether the evaluation was performed using However, several studies with smaller numbers of patients
paired samples. After the initial selection, full-text articles (<50) were included for data aggregation. The study by

Volume 9 Issue 3 (2025) 66 doi: 10.36922/EJMO025150101