Expression Patterns of Coagulation Factor XIII Subunit A on Leukemic Lymphoblasts Correlate with Clinical Outcome and Genetic Subtypes in Childhood B-cell Progenitor Acute Lymphoblastic Leukemia

Abstract

Background: Based on previous retrospective results, we investigated the association of coagulation FXIII subunit A (FXIII-A) expression pattern on survival and correlations with known prognostic factors of B-cell progenitor (BCP) childhood acute lymphoblastic leukemia (ALL) as a pilot study of the prospective multi-center BFM ALL-IC 2009 clinical trial. Methods: The study included four national centers (n = 408). Immunophenotyping by flow cytometry and cytogenetic analysis were performed by standard methods. Copy number alteration was studied in a subset of patients (n = 59). Survival rates were estimated by Kaplan-Meier analysis. Correlations between FXIII-A expression patterns and risk factors were investigated with Cox and logistic regression models. Results: Three different patterns of FXIII-A expression were observed: negative (<20%), dim (20–79%), and bright (≥80%). The FXIII-A dim expression group had significantly higher 5-year event-free survival (EFS) (93%) than the FXIII-A negative (70%) and FXIII-A bright (61%) groups. Distribution of intermediate genetic risk categories and the “B-other” genetic subgroup differed significantly between the FXIII-A positive and negative groups. Multivariate logistic regression confirmed independent association between the FXIII-A negative expression characteristics and the prevalence of intermediate genetic risk group. Conclusions: FXIII-A negativity is associated with dismal survival in children with BCP-ALL and is an indicator for the presence of unfavorable genetic alterations.

Clinical Proteomics of Biofluids in Haematological Malignancies

“…A recent study by Bories et al used a chromatographic separation technique developed by Poinsignon et al in order to establish individual reference values for each enantiomer to facilitate routine clinical use of serum 2-HG as a biomarker for disease monitoring in AML [ 84 , 85 ]. In acute lymphoblastic leukemia (ALL), various serum proteins have been identified in recent years as candidate biomarkers including S100A8, coagulation factor XIII subunit A, and a panel of 9 serum-derived glycoproteins [ 86 , 87 , 88 ]. Studies incorporating larger cohorts and clinically relevant workflows are required to bring “potential” and “candidate” serum biomarkers from benchtop to clinical use, a difficult task in certain cases due to low reproducibility, a lack of method standardisation, and difficulties translating the test used during discovery to a clinical-grade technology [ 89 ].…”

Coagulation Factor XIII Subunit A Is a Biomarker for Curative Effects and Prognosis in Malignant Solid Tumors, Especially Non-small Cell Lung Cancer

“…In recent years, the expression of FXIII-A was found to be significantly upregulated in some types of cancer cells and tumor-associated macrophages (TAMs). The expression of FXIII-A was increased in acute myelomonocytic leukemia, acute monocytic leukemia and acute promyelocytic leukemia, suggesting that FXIII-A might be used as a biomarker for differentiating myeloblastic and monoblastic leukemias (3,4) and for prognostic risk stratification (5)(6)(7). Kiss, F et al reported that normal lymphoid precursors and mature lymphocytes do not contain FXIII-A, but the expression of FXIII-A in B cell acute lymphoblastic leukemia cells is significantly increased (8).…”