MACROPHAGE POLARIZATION AND CD47 BLOCKADE IN PTPN11-MUTATED JUVENILE MYELOMONOCYTIC LEUKEMIA

Genetic findings revealed germline SAMD9L mutations in three patients and GATA2 mutations in two.Monosomy 7 was also detected in three patients, often co-occurring with these germline mutations.According to MDS subtypes, 8 patients were diagnosed with MDS, one with MDS with excess blasts (MDS-EB), one with MDS progressing to acute myeloid leukemia (MDS-AML), and one with secondary MDS.The clinical course was marked by a high transfusion burden.Of three patients who underwent bone marrow transplantation, two remain in remission.Patients with advanced disease, MDS-EB or MDS-AML, were refractory to standard therapies, including azacitidine, venetoclax, and induction chemotherapy.Conclusions: SAMD9L and GATA2 mutations are prominent drivers in this pediatric MDS cohort, frequently associated with high-risk monosomy 7. The poor response to therapy in advanced stages underscores that early diagnosis is critical for improving treatment success.The authors strongly recommend that children presenting with chronic cytopenia and significant bone marrow dysplasia undergo comprehensive cytogenetic and genetic testing to facilitate timely diagnosis and intervention.