Prognostic Score for CML Blast Phase and New Biomarkers in AML and T-ALL
A CML blast phase prognostic score separates patients into three risk groups with distinct survival. Separate AML studies identified circRNA and NFS1/GSDMD biomarkers; a T-ALL study highlighted markers including CD38, CD99, and TRBC1.
A new prognostic scoring system for chronic myeloid leukemia (CML) in blast phase, developed from 275 patients in the European LeukemiaNet Blast Phase Registry, stratifies patients into three risk groups with markedly different overall survival. In separate studies, researchers also identified novel prognostic biomarkers in acute myeloid leukemia and T-cell acute lymphoblastic leukemia.
Currently there is no established prognostic scoring system for CML in blast phase, a stage associated with poor outcomes and significant clinical heterogeneity. The study used a Cox proportional hazards model and identified six independent prognostic factors present at the onset of blast phase: blast percentage, platelet count, age, immunophenotype, extramedullary disease, and previous history of CML. These variables were integrated into a scoring system that divided patients into low-, intermediate-, and high-risk groups. The low-risk group, representing 14% of patients, had a median overall survival of 97 months; the intermediate-risk group (59% of patients) had a median overall survival of 22 months; and the high-risk group (27% of patients) had a median overall survival of 9 months. The cohort had a median observation time of 45 months and a median overall survival of 18.9 months. Cross-validation indicated good performance of the score, though the authors strongly recommend external validation.
In acute myeloid leukemia, two independent lines of research have advanced biomarker discovery. One study analyzed RNA-sequencing data from 315 Swedish AML patients and identified 5,711 high-confidence circular RNAs (circRNAs), including 402 differentially expressed between AML and healthy controls. High expression of hsa_circ_0024048 and hsa_circ_0084678 was associated with significantly improved overall survival, a relationship not observed in their host genes, and both circRNAs were linked to drug sensitivities in external datasets. Another AML study found that higher expression of the ferroptosis-related gene NFS1 and lower expression of the pyroptosis-related gene GSDMD correlated with poor prognosis and decreased one-year survival in AML patients.
In T-cell acute lymphoblastic leukemia, a flow cytometry-based study delineated the expression patterns of CD38, CD99, CD127, CD135, CD147, and TRBC1 across T-ALL subtypes. The study discusses the synergistic effects of anti-CD38 monoclonal antibodies with chemotherapy, highlights the role of CD99 in central nervous system involvement, shows the sensitivity of CD127 expression to specific therapies, and explores CD135 as a potential therapeutic antigen. Combining TRBC1, CD127, or CD99 with existing markers may help differentiate reactive or malignant T cells, refine T-ALL subtype classification, and monitor CNS protection during therapy. The study also presents evidence supporting anti-CD38, anti-CD99, anti-CD147, and anti-TRBC1 CAR-T cell therapies in improving treatment outcomes for T-ALL.