CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage

L Slamova; J Starkova; E Fronkova; M Zaliova; L Reznickova; F W van Delft; E Vodickova; J Volejnikova; Z Zemanova; K Polgarova; G Cario; M Figueroa; T Kalina; K Fiser; J P Bourquin; B Bornhauser; M Dworzak; J Zuna; J Trka; J Stary; O Hrusak; E Mejstrikova

doi:10.1038/leu.2013.354

Back

CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage

Journal article

Peer reviewed

CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage

L Slamova, J Starkova, E Fronkova, M Zaliova, L Reznickova, F W van Delft, E Vodickova, J Volejnikova, Z Zemanova, K Polgarova, …

Leukemia, Vol.28(3), pp.609-620

2014-03

DOI: https://doi.org/10.1038/leu.2013.354

PMID: 24270736

Abstract

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology

Prognosis

Humans

Child, Preschool

Immunophenotyping

Male

Multiplex Polymerase Chain Reaction

Neoplasm, Residual

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology

Cell Lineage

Adolescent

Monocytes - pathology

Female

Child

CD2 Antigens - immunology

Cohort Studies

Switches from the lymphoid to myeloid lineage during B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment are considered rare and thus far have been detected in MLL-rearranged leukemia. Here, we describe a novel BCP-ALL subset, switching BCP-ALL or swALL, which demonstrated monocytosis early during treatment. Despite their monocytic phenotype, 'monocytoids' share immunoreceptor gene rearrangements with leukemic B lymphoblasts. All swALLs demonstrated BCP-ALL with CD2 positivity and no MLL alterations, and the proportion of swALLs cases among BCP-ALLs was unexpectedly high (4%). The upregulation of CEBPα and demethylation of the CEBPA gene were significant in blasts at diagnosis, prior to the time when most of the switching occurs. Intermediate stages between CD14(neg)CD19(pos)CD34(pos) B lymphoblasts and CD14(pos)CD19(neg)CD34(neg) 'monocytoids' were detected, and changes in the expression of PAX5, PU1, M-CSFR, GM-CSFR and other genes accompanied the switch. Alterations in the Ikaros and ERG genes were more frequent in swALL patients; however, both were altered in only a minority of swALLs. Moreover, switching could be recapitulated in vitro and in mouse xenografts. Although children with swALL respond slowly to initial therapy, risk-based ALL therapy appears the treatment of choice for swALL. SwALL shows that transdifferentiating into monocytic lineage is specifically associated with CEBPα changes and CD2 expression.

Metrics

9 Record Views

35 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.103 Blood Disorders; 1.103.155 Acute Myeloid Leukemia
Web Of Science research areas: Hematology; Oncology
ESI research areas: Clinical Medicine

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage
Creators: L Slamova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
J Starkova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
E Fronkova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
M Zaliova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
L Reznickova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
F W van Delft - Northern Institute for Cancer Research, Newcastle University, Newcastle, UK
E Vodickova - Department of Clinical Hematology, University Hospital Motol, Prague, Czech Republic
J Volejnikova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
Z Zemanova - Centre of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
K Polgarova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
G Cario - Department of Pediatrics, University Hospital Schleswig Holstein, Kiel, Germany
M Figueroa - University of Michigan Medical School, Department of Pathology, Ann Arbor, MI, USA
T Kalina - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
K Fiser - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
J P Bourquin - Division of Oncology and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland
B Bornhauser - Division of Oncology and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland
M Dworzak - Children's Cancer Research Institute and St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria
J Zuna - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
J Trka - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
J Stary - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
O Hrusak - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
E Mejstrikova - Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
Publication Details: Leukemia, Vol.28(3), pp.609-620
Academic Unit: Miller School of Medicine; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 24270736
Record Identifier: 991031599037202976