Abstract
Previously we identified B-cell lineage leukemic lymphoblasts as a new expression site for subunit A of blood coagulation factor XIII (FXIII-A). On the basis of FXIII-A expression, various subgroups of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be identified. Fifty-five children with BCP-ALL were included in the study. Bone marrow samples were obtained by aspiration and the presence of FXIII-A was detected by flow cytometry. G-banding and fluorescent in situ hybridization was performed according to standard procedures. The 10-year event-free survival (EFS) and overall survival (OS) rate of FXIII-A-positive and FXIII-A-negative patients showed significant differences (EFS: 84% vs. 61%, respectively; p = 0.031; OS: 89% vs. 61%; p = 0.008). Of all the parameters examined, there was correlation only between FXIII-A expression and ‘B-other’ genetic subgroup. Further multivariate Cox regression analysis of FXIII-subtype and genetic group or ‘B-other’ subgroup identified the FXIII-A negative characteristic as an independent factor associated with poor outcome in BCP-ALL. We found an excellent correlation between long-term survival and the FXIII-A-positive phenotype of BCP lymphoblasts at presentation. The results presented seem to be convincing enough to suggest a possible role for FXIII-A expression in the prognostic grouping of childhood BCP-ALL patients.
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Acknowledgements
The authors thank Dr. Erzsébet Balogh for performing the cytogenetic analyses and Csaba Antal for his administrative help. They are also grateful to all the physicians and assistants participating in the clinical care of patients and in the execution of flow cytometry investigations at the departments of the University of Debrecen. The authors express their gratitude to Dr. Kálmán Nagy and their coworkers at the Borsod-Abaúj-Zemplén County Hospital and University Hospital for providing bone marrow samples for flow cytometric analysis. Finally, they thank Attila Kárai for proofing and editing the manuscript. This study was supported by an OTKA K-108885 grant (CsK).
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Online Resource 1
The prognostic value of ‘B-other’ characteristics in children with B-cell precursor ALL. When analyzed by Kaplan-Meier plots, significant difference was found in overall survival (p = 0.021), and a tendency in event-free survival between children with ‘B-other’ characteristics and those with recurrent genetic alterations. (PDF 94.4 kb)
Online Resource 2
Investigation of the prognostic impact of ‘B-other’ characteristics and that of FXIII-A manifestation by multivariate Cox regression analyses. In the Cox model, including either parameter and adjusting initial prognostic parameters (age and WBC) FXIII-A character had the most potent, significant effect on overall survival (HR: 4.8; 95% CI: 1.2–19.2; p = 0.025) (PDF 81.3 kb)
Online Resource 3
The prognostic value of MRD in bone marrow on day 15 in children with B-cell precursor ALL. Kaplan-Meier plots of event-free (a) and overall survival (b) of the various prognostic groups based on MRD classification by flow cytometric analysis. Significant difference was found between flow-medium-risk (FMR) and flow-high-risk (FHR) group both in terms of event-free and overall survival (p = 0.01 and p = 0.004). (PDF 18.7 kb)
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Kárai, B., Hevessy, Z., Szánthó, E. et al. Expression of Coagulation Factor XIII Subunit A Correlates with Outcome in Childhood Acute Lymphoblastic Leukemia. Pathol. Oncol. Res. 24, 345–352 (2018). https://doi.org/10.1007/s12253-017-0236-0
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DOI: https://doi.org/10.1007/s12253-017-0236-0