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

Lookup NU author(s): Dr Frederik van DelftORCiD

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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 CEBPa 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 CEBPa changes and CD2 expression.


Publication metadata

Author(s): Slamova L, Starkova J, Fronkova E, Zaliova M, Reznickova L, van Delft FW, Vodickova E, Volejnikova J, Zemanova Z, Polgarova K, Cario G, Figueroa M, Kalina T, Fiser K, Bourquin JP, Bornhauser B, Dworzak M, Zuna J, Trka J, Stary J, Hrusak O, Mejstrikova E

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2014

Volume: 28

Issue: 3

Pages: 609-620

Print publication date: 17/01/2014

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2013.354

DOI: 10.1038/leu.2013.354


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Funding

Funder referenceFunder name
Kay Kendall Leukaemia Fund
00064203project for conceptual development of research organization
CZ.2.16/3.1.00/24022EU
CZ.2.16/3.1.00/24022project for conceptual development of research organization
GACR P301/10/1877
GAUK 914613
NT 12397-4
NT13462
RVO-VFN64165/2012
Sciex 09.043

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