Abstract
Objective: To summarize the clinical characteristics, treatment
effects and survival outcomes of children with NF1 mutation-positive acute leukemia. Methods : The clinical data
and prognosis of 28 patients with NF1 mutation-positive acute
leukemia treated at Beijing Children’s Hospital, Capital Medical
University, between January 2017 and February 2024 were retrospectively
analyzed. Results : A total of 28 patients were included in the
study, with a median follow-up of 16 (1.2–85.5) months. Twelve patients
had acute lymphoblastic leukemia, of whom 75.0% were at intermediate
risk. Complete response (CR) was achieved in the bone marrow after
induction chemotherapy, with a minimal residual disease (MRD) of
1×10-3 at Day 33. Fifteen patients had acute myeloid
leukemia (AML), of whom 66.7% were at high risk. The CR rate in the
bone marrow was 86.6% at Day 28. Eleven (73.3%) patients survived at
the end of follow-up. One patient with acute promyelocytic leukemia had
standard risk and a good response. The overall survival rate of children
with NF1 mutations was comparable to that of children with no
mutations. However, children with germline NF1 mutations had a
poor prognosis compared with those with somatic mutations, especially in
AML patients. The frequency of NF1 mutations was 2–87.7%. The
clinical manifestations of 3 patients with neurofibromatosis included
café-au-lait macules, freckles, xanthogranuloma, scoliosis, and benign
intracranial lesions. Conclusion: Most NF1 mutations in
children with acute leukemia are somatic mutations that do not affect
overall survival. Children with leukemia complicated with
neurofibromatosis should undergo lifelong follow-up.
Leukemia is the most common cancer and major cause of death in
childhood, and chromosomal abnormalities or genetic events such as gene
mutations and fusion genes occur over the course of the disease.NF1 is a tumor suppressor gene and a negative regulator of the
RAS pathway. Mutations in this gene may lead to neurofibromatosis type 1
(OMIM 613113). In addition, the risk of benign and malignant tumors is
increased. Among pediatric hematological diseases, NF1 mutations
are frequently observed in juvenile myelomonocytic leukemia
(JMML)1. Moreover, these mutations are associated with
the pathogenesis of JMML and its poor clinical prognosis. However, there
are few reports on this gene in pediatric acute leukemia. Data on the
clinical characteristics, treatment effects and prognosis of patients
with NF1 mutation-positive acute leukemia are lacking. In this
study, the clinical and molecular biological characteristics, treatment
effects and survival status of 28 children with NF1 mutation-positive acute leukemia were retrospectively collected and
analyzed to provide a reference for clinical diagnosis and treatment.