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.

Bettina Kárai,Eszter Szánthó,Łukasz Sędek,Karin Nebral,Andishe Attarbaschi,Michael Dworzak,István Szegedi,Ágnes Vojczek,Oskar A Haas,Angela Schumich,Réka Simon,Gábor Barna,Judit Müller,János Kappelmayer,Katalin Gyurina,Csongor Kiss,Pál Jáksó,Zsuzsanna Hevessy,Gabòr Kovàcs ,Attila Nagy ,Tomasz Szczepański ,Anikó Újfalusi ,Alexandra Kolenová ,Peter Švec ,Jerzy Kowalczyk ,L Tiszlavicz

doi:10.3390/cancers12082264

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.

Highlights

Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disorder in children, which was virtually incurable before the 1960-ies
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
Using oligonucleotide microarray analysis and RT-Q-PCR method, we have demonstrated that the intensity of expression of the FXIII-A1 gene (F13A1) at the mRNA level correlated with the three characteristic FXIII-A protein expression groups defined by flow cytometry (FC), i.e., FXIII-A-negative, -dim, and –bright

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disorder in children, which was virtually incurable before the 1960-ies. The ALL IC-BFM 2002 clinical trial demonstrated successful co-operation of the participating groups resulting in competent event-free survival (EFS) and overall survival (OS) rates which exceeded historical results of the members [4]. 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). Correlations between FXIII-A expression patterns and risk factors were investigated with Cox and logistic regression models. The FXIII-A dim expression group had significantly higher 5-year event-free survival (EFS)

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