"Pediatric Myeloid Neoplasms: New Insights into Diagnosis, Prognosis, and Treatment"

Viviane Lamim Lovatel¹Jeffrey J Pu²Teresa de Souza Fernandez^1*

• ¹National Cancer Institute (INCA), Rio de Janeiro, Brazil
• ²Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

Unlike in adults, childhood myeloid neoplasms are rare and diverse diseases of clonal hematopoietic cell origin. These neoplasms exhibit distinct clinical, morphological, and genetic features, which require a specialized pediatric approach (1). These differences also influence diagnostic criteria and disease management, emphasizing the need for tailored recommendations (2).Among myeloid neoplasms in children, acute myeloid leukemia (AML) is the most common, accounting for about 20% of childhood leukemia. However, other myeloid neoplasms, such as myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), chronic myeloid leukemia (CML), and Langerhans cell histiocytosis (LCH), are much rarer, each comprising less than 5% of pediatric hematologic malignancies. In MDS, the subtype refractory cytopenia of childhood (RCC) is observed in approximately 60% of cases and is a well-recognized form of bone marrow failure, characterized by persistent cytopenia and dysplasia. JMML, on the other hand, is marked by constitutive activation of the RAS signal transduction pathway. CML is defined by the presence of the BCR::ABL1 fusion gene, which leads to leukocytosis (3, 4).This research topic aimed to highlight recent advances in the clinical and biological aspects of pediatric patients with myeloid neoplasms. It features four articles: one on LCH and three discussing pediatric AML treatment, novel biomarkers, and recent advancements in the literature. Wan et al. reported a case of LCH, a myeloid neoplasm characterized by activating mutations in the mitogen-activated protein kinase (MAPK) pathway. In this study, the patient experienced an unusual accumulation of mononuclear phagocytes infiltrating the stomach, which was initially misdiagnosed as gastric lymphoma.The diagnosis of pediatric myeloid neoplasms can be challenging due to their heterogeneity and overlapping clinical symptoms with other conditions. Moreover, therapeutic options for most pediatric myeloid neoplasms remain limited. For many of these conditions, allogeneic hematopoietic stem cell transplantation remains the primary, and often the only, potentially curative treatment (4, 5).Nevertheless, significant progress in the prognosis of AML has been made over the last 25 years, as highlighted by Rao et al. in this research topic. This progress has been largely due to the integration of genetic, immunological, transcriptomic, and epigenomic markers. In this context, Bakhtiari et al. utilized a single-cell approach to describe a novel marker, ARMH1, for pediatric AML. High ARMH1 expression was observed in blast cells from patients who had disease relapse or a high-risk cytogenetic profile. ARMH1 expression was associated with poor outcomes and impacted cell proliferation by reducing key cell cycle regulators.Rao et al. also emphasized, in their bibliometric analysis, that advancements in knowledge and treatment are primarily confined to developed countries. They noted that global collaboration and the application of advanced tools are essential for personalized medicine and the discovery of new therapeutic targets. Furthermore, Pawiińska-Wąsikowska et al. stressed the importance of well-assessed clinical features and adequate supportive care for effective clinical management. Their study revealed that treatment-related mortality in AML cases was more strongly associated with hyperleukocytosis, particularly valuable in developing nations where new treatments and personalized medicine technologies may be inaccessible due to high costs.Given the many challenges associated with childhood myeloid neoplasms, continued research is crucial for better understanding these diseases' unique characteristics and ultimately improving patient outcomes. This editorial commentary highlights recent developments in the pathology of these complex neoplasms. By exploring novel discoveries, we hope to foster a deeper understanding of these conditions and drive progress toward more effective diagnostic and therapeutic strategies specifically for pediatric patients with myeloid neoplasms.