Xikun Liu

The bone marrow tumor microenvironment (TME) is critical for acute myeloid leukemia (AML) progression, immune evasion, and treatment resistance. SRC, a non-receptor tyrosine kinase involved in multiple oncogenic pathways, has not been systematically characterized in AML in relation to prognosis and immune regulation. We integrated bulk transcriptomic and single-cell RNA-sequencing datasets from TCGA, BeatAML, and GEO. Immune-related targets were identified using xCell-based immune scoring and weighted gene co-expression network analysis (WGCNA), followed by protein–protein interaction analysis and multi-algorithm machine-learning screening. We then evaluated SRC expression patterns, prognostic associations, immune microenvironment features, predicted drug sensitivity, single-cell differentiation dynamics, intercellular communication, and in silico virtual knockout perturbation (scTenifoldKnk). SRC emerged as the most robust hub gene after integration of WGCNA, PPI analysis, machine-learning feature selection, and survival screening. SRC was significantly upregulated in AML compared with normal controls and was independently associated with poor overall survival (HR = 1.231, p = 0.037). High SRC expression was linked to adverse ELN/FAB features, increased immune checkpoint expression, enrichment of inflammatory and immunoregulatory pathways, and a higher proportion of primitive leukemia-associated cell states. Single-cell analyses further suggested that SRC was enriched in CD34⁺ progenitor compartments, associated with altered cell–cell communication, and accompanied by distinct mutation and pathway profiles. Drug-response prediction and in silico network perturbation analysis further supported the potential biological and translational relevance of SRC-centered programs. SRC is a prognostically relevant and immune-associated hub linked to AML microenvironment remodeling, and may serve as a candidate biomarker and potential therapeutic target that warrants further experimental validation.

Chronic myeloid leukemia (CML) is characterized by the BCR::ABL1 fusion gene, resulting from Philadelphia (Ph) chromosome rearrangements that generate abnormal t (9; 22)(q34;q11) translocations. The most common fusion variants are e13a2 and e14a2. We diagnosed a case of CML with the rare e8a2 fusion variant using real-time quantitative PCR and sequencing. Although the e8a2 variant is increasingly reported in CML, comprehensive retrospective analyses remain scarce. Through a systematic review of published e8a2 BCR::ABL1 cases, we summarized the classification, treatment outcomes, and prognostic characteristics associated with this rare genotype. This analysis aims to provide additional evidence to facilitate improved diagnosis and therapeutic strategies for e8a2-positive CML patients.