Page 77 - EJMO-9-3

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

All studies were cohort designs and evaluated using the These findings have therapeutic implications and can
Newcastle-Ottawa Quality Assessment Scale (Table 2). impact patient survival. In some cases, identifying a newly
acquired mutation could provide eligibility for the only
4. Discussion potentially curative option in relapsed or refractory AML

The present study is the first systematic review and meta- (i.e., bone marrow transplantation).
analysis investigating FLT3 mutational shifts in AML, This discrepancy may be associated with inherent
incorporating data from over 1,000 patients. The prevalence limitations of the detection method itself. It is well known
of FLT3 mutations observed aligned with previous reported that molecular technologies have improved over the years.
rates in the literature. Notably, our analysis revealed that Currently, the most recommended PCR method for FLT3
approximately one in seven patients exhibited a change analysis is fragment analysis. In our evaluation, some
in FLT3 mutation status between diagnosis and relapse or older studies used gel-based PCR as the detection method,
refractory disease. Such a frequency is not negligible and which has lower sensitivity. It is also important to consider
reinforces the recommendation for molecular reassessment the possibility of false negatives. PCR is a method that
at multiple time points during the disease course. The has difficulty detecting very short fragments, identifying
increasing use of mutation-guided therapies in AML mutations in previously undescribed regions, and provides
underscores the need for accurate and dynamic mutational only limited information, such as size, number, and allelic
profiling. Identifying the emergence or loss of actionable burden. It does not provide additional details about the
mutations can prevent the administration of potentially sequence or its specific location, nor can it distinguish
toxic therapies with limited benefit in mutation-negative between homozygous and heterozygous mutations.
patients, and conversely, guide the appropriate use of Nevertheless, PCR is a more accessible method compared
targeted agents in those who acquire relevant mutations. to NGS and yields results more rapidly. Therefore, the
sensitivity of the technique may influence the findings.
Table 2. Newcastle–Ottawa Scale quality assessment scores Another contributing factor is the nature of the
for included studies mutation itself. Some studies suggest that FLT3 mutations
Study Selection Comparability Outcome References may emerge later in the course of AML, following a
Shih et al. **** * *** 45 branched clonal evolution model. This may occur due to
external factors, such as chemotherapy or alterations in
Nazha et al. **** * ** 43 the bone marrow microenvironment. For example, a new
Shih et al. **** * *** 38 subclone or one that was present at undetectable levels may
Nakano et al. **** * *** 37 acquire a selective advantage over other clones, leading to
McCormick et al. **** * *** 33 its proliferation and potential dominance. Alternatively,
Cloos et al. **** * *** 30 the mutation may already be the predominant clone at
Palmisano et al. **** * *** 31 diagnosis. In such cases, it may be eliminated by treatment
Suzuki et al. **** * *** 32 or reduced to levels below the detection limit.
Tiesmeier et al. **** * *** 28 There is an ongoing debate in the literature regarding
Kottaridis et al. **** * *** 26 the utility of FLT3 as a measurable residual disease marker
Schnittger et al. ** * *** 32 and its prognostic significance in AML. The previously
described instability in its mutational status limits its
Gourdin et al. **** * *** 44 application for MRD monitoring.
Janke et al. **** * ** 36 Some studies have suggested that the acquisition of
Wakita et al. **** * *** 35
FLT3 mutations in relapsed AML is associated with an
Park et al. **** ** *** 40 adverse prognosis, with outcomes comparable to patients
46
Wang et al. *** ** *** 34 who remain FLT3-mutated at both diagnosis and relapse.
Schnittger et al. **** ** *** 32 Notably, the absence of FLT3 mutations at relapse has been
Bachas et al. *** * *** 42 associated with a more favorable prognosis when compared
9
Abdelhamid et al. *** * *** 41 to patients who remain FLT3-mutated. In the current
Nakamura et al. * * ** 27 review, it was not possible to evaluate clinical outcomes
such as overall survival, as only a minority of studies
Notes: The Newcastle–Ottawa Quality Assessment Scale checklists reported this information. Furthermore, data regarding
adapted for cross-sectional and cohort studies. *Asterisks correspond
to ratings assigned for each item according to The Newcastle–Ottawa cytogenetic and cytomorphologic changes were insufficient
Quality Assessment Scale. for analysis, as these parameters were not mandatory

Volume 9 Issue 3 (2025) 69 doi: 10.36922/EJMO025150101