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Leukemia. 2014 Mar;28(3):609-20. doi: 10.1038/leu.2013.354. Epub 2013 Nov 25.

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

Author information

1
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
2
Northern Institute for Cancer Research, Newcastle University, Newcastle, UK.
3
Department of Clinical Hematology, University Hospital Motol, Prague, Czech Republic.
4
Centre of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
5
Department of Pediatrics, University Hospital Schleswig Holstein, Kiel, Germany.
6
University of Michigan Medical School, Department of Pathology, Ann Arbor, MI, USA.
7
Division of Oncology and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
8
Children's Cancer Research Institute and St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.

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.

PMID:
24270736
DOI:
10.1038/leu.2013.354
[Indexed for MEDLINE]

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