CSF3R Mutations Imply Adverse Prognostic Impact in Adult Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

BACKGROUND

Activating colony-stimulating factor 3 receptor (CSF3R) mutations are uncommon in acute myeloid leukemia (AML), and their prognostic significance remains unclear.

METHODS

We compared clinical, treatment response, and survival data between CSF3R-mutated and CSF3R-wild-type AML patients.

RESULTS

CSF3R-mutated cases presented a distinct molecular profile, with T618I and T640A being the most frequent variants. Common molecular aberrations included CEBPA bZip mutations (40%) and CBF fusions (23%), as well as secondary-type AML-associated mutations such as those in ASXL1, SRSF2, and EZH2. In contrast, NPM1 mutations were significantly less common in CSF3R-mutated patients (p = 0.03). Induction responses were poorer in CSF3R-mutated AML patients, with lower complete remission (55.6% vs. 78.8%, p = 0.004), reduced measurable residual disease (MRD) negativity (53.3% vs. 87.6%, p < 0.001), and shorter MRD maintenance duration (5.4 vs. 21.6 months, p < 0.001). According to the logistic regression analysis, CSF3R mutation emerged as an independent predictor of induction failure (p < 0.001). Survival outcomes were also inferior: the median overall survival (OS) was 20.7 months versus not reached (p = 0.0013), and progression-free survival was 9.4 versus 63.6 months (p < 0.0001). The adverse impact of CSF3R mutations was most pronounced in CEBPA bZip AML. CSF3R mutations abrogated the expected favorable prognosis (3-year OS: 44.2% vs. 88.2%, p = 0.0008). Conversely, CSF3R status did not affect outcomes in CBF-rearranged patients (p = 0.70).

CONCLUSIONS

CSF3R mutations define a distinct, high-risk AML subset characterized by an inferior treatment response and survival, warranting incorporation into future risk stratification.