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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, FW. van Delft, E. Vodickova, J. Volejnikova, Z. Zemanova, K. Polgarova, G. Cario, M. Figueroa, T. Kalina, K. Fiser, JP. Bourquin, B. Bornhauser, M. Dworzak, J. Zuna, J. Trka, J....

. 2014 ; 28 (3) : 609-620.

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem, validační studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc14063832

Grantová podpora
NT12397 MZ0 CEP - Centrální evidence projektů
NT13462 MZ0 CEP - Centrální evidence projektů

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.

Citace poskytuje Crossref.org

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$a CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage / $c L. Slamova, J. Starkova, E. Fronkova, M. Zaliova, L. Reznickova, FW. van Delft, E. Vodickova, J. Volejnikova, Z. Zemanova, K. Polgarova, G. Cario, M. Figueroa, T. Kalina, K. Fiser, JP. Bourquin, B. Bornhauser, M. Dworzak, J. Zuna, J. Trka, J. Stary, O. Hrusak, E. Mejstrikova,
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$a 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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$a Polgarova, K $u Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
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