FOS and FOSB are linked with CNS-infiltration and inferior prognosis in childhood T-cell acute lymphoblastic leukemia

L Spory; L Lenk; D Winterberg; A Alsadeq; M Carlet; I Jeremias; G Cario; M Schrappe; M Vossen-Gajcy; DM Schewe

doi:10.1055/s-0039-1687155

Klinische Pädiatrie, Inhaltsverzeichnis

Klin Padiatr 2019; 231(03): 164
DOI: 10.1055/s-0039-1687155

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

FOS and FOSB are linked with CNS-infiltration and inferior prognosis in childhood T-cell acute lymphoblastic leukemia

L Spory

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

L Lenk

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

D Winterberg

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

A Alsadeq

²Institute of Immunology, Ulm University Medical Center, Ulm, Germany

,

M Carlet

³Helmholtz Zentrum München, Department of Gene Vectors, Research Center for Environmental Health, Munich, Germany

,

I Jeremias

³Helmholtz Zentrum München, Department of Gene Vectors, Research Center for Environmental Health, Munich, Germany

,

G Cario

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

M Schrappe

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

M Vossen-Gajcy

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

,

DM Schewe

¹Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany

› Institutsangaben

Abstract

Volltext

Aim:

CNS involvement in ALL is a major clinical challenge, particularly in T-ALL. Novel targets to reliably detect and eradicate CNS-leukemia are urgently needed.

Methods:

Comparative RNA-sequencing was performed with patient derived xenograft TALL blasts recovered from the bone marrow (BM) and the CNS of NSG-mice. FOS and FOSB mRNA were measured in diagnostic bone marrow samples of 112 pediatric T-ALL patients and correlated with clinical parameters.

Results:

The AP-1 genes FOS and FOSB were significantly upregulated in blasts recovered from the CNS versus BM of NSG-mice. Accordingly, CNS+ patients exposed significantly elevated FOSB-mRNA levels as compared to CNS- patients (p = 0.038). Furthermore, FOShigh and FOSBhigh patients (mRNA levels above median) showed significantly lower 5-year event free survival (p = 0.031 and p = 0.011, respectively) than FOSlow and FOSBlow patients. Importantly, 6/9 patients with CNS-relapse were FOShigh and FOSBhigh upon diagnosis.

Conclusion:

FOS and FOSB may be novel independent predictors of prognosis and surrogate markers with therapeutic potential for CNS-infiltration and relapse in T-ALL requiring further prospective and mechanistic validation.