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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.

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


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.

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