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Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA), is a rare but potentially life-threatening disease characterized by pancytopenia and a hypocellular bone marrow. Pulmonary mucormycosis (PM) is a rare but life-threatening fungal infection observed in immunocompromised patients, particularly those with neutropenia and those using corticosteroids, with a high mortality rate from 40 to 80%. However, PM diagnosis and treatment remain challenging. This study reports a case of very severe aplastic anemia (VSAA) in a male child with PM. The innovation of this article lies in the following aspects: the patient exhibited typical clinical manifestations, the reverse halo sign (RHS) on chest computed tomography (CT), and a positive metagenomic next-generation sequencing (mNGS) analysis; despite aggressive anti-infective treatment and left lower lobectomy, he experienced a poor clinical outcome. Reflecting on cases with poor prognosis can indeed offer valuable insights and opportunities for learning. This study underlines the diagnostic challenges in mucormycosis, which should be considered in persistent fever that is unresponsive to standard antibiotic and antifungal therapies, and conduct a comprehensive examination to achieve early detection, diagnosis and treatment. It was concluded that, in addition to antifungal treatment, early surgery is essential for treating mucormycosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Huang, Jiang, Ren, Peng and Wu.)