title: CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Slamova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Starkova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Fronkova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Zaliova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Reznickova
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle, UK.
authors.forename: F W
authors.initials: FW
authors.lastname: van Delft
authors.affiliation: Department of Clinical Hematology, University Hospital Motol, Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Vodickova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Volejnikova
authors.affiliation: Centre of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Zemanova
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Polgarova
authors.affiliation: Department of Pediatrics, University Hospital Schleswig Holstein, Kiel, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Cario
authors.affiliation: University of Michigan Medical School, Department of Pathology, Ann Arbor, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Figueroa
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Kalina
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Fiser
authors.affiliation: Division of Oncology and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: Bourquin
authors.affiliation: Division of Oncology and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Bornhauser
authors.affiliation: Children's Cancer Research Institute and St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Dworzak
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Zuna
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Trka
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Stary
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Hrusak
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Mejstrikova
mesh_terms: D000293:Adolescent; D018801:CD2 Antigens / Q000276:immunology*; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D009000:Monocytes / Q000473:pathology*; D060885:Multiplex Polymerase Chain Reaction; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology; D011379:Prognosis
chemical_list: D018801:CD2 Antigens