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, F. W. Van Delft, E. Vodickova, J. Volejnikova, Z. Zemanova, K. Polgarova, G. Cario, Maria Figueroa, T. Kalina, K. Fiser, J. P. Bourquin, B. Bornhauser, M. Dworzak, J. Zuna, J. Trka, J. Stary & 2 others O. Hrusak, E. Mejstrikova

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)609-620
Number of pages12
JournalLeukemia
Volume28
Issue number3
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Switch Genes
B-Lymphocyte Subsets
Therapeutics
Gene Rearrangement
Heterografts
Genes
Leukemia
Up-Regulation
Phenotype

Keywords

  • Acute lymphoblastic leukemia
  • CCAAT/enhancer-binding protein alpha
  • CD2 Antigen
  • Lineage switch
  • Minimal residual disease
  • Monocytes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Slamova, L., Starkova, J., Fronkova, E., Zaliova, M., Reznickova, L., Van Delft, F. W., ... Mejstrikova, E. (2014). CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia, 28(3), 609-620. https://doi.org/10.1038/leu.2013.354

CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. / Slamova, L.; Starkova, J.; Fronkova, E.; Zaliova, M.; Reznickova, L.; Van Delft, F. W.; Vodickova, E.; Volejnikova, J.; Zemanova, Z.; Polgarova, K.; Cario, G.; Figueroa, Maria; Kalina, T.; Fiser, K.; Bourquin, J. P.; Bornhauser, B.; Dworzak, M.; Zuna, J.; Trka, J.; Stary, J.; Hrusak, O.; Mejstrikova, E.

In: Leukemia, Vol. 28, No. 3, 01.01.2014, p. 609-620.

Research output: Contribution to journalArticle

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 2014, 'CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage', Leukemia, vol. 28, no. 3, pp. 609-620. https://doi.org/10.1038/leu.2013.354
Slamova L, Starkova J, Fronkova E, Zaliova M, Reznickova L, Van Delft FW et al. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia. 2014 Jan 1;28(3):609-620. https://doi.org/10.1038/leu.2013.354
Slamova, L. ; Starkova, J. ; Fronkova, E. ; Zaliova, M. ; Reznickova, L. ; Van Delft, F. W. ; Vodickova, E. ; Volejnikova, J. ; Zemanova, Z. ; Polgarova, K. ; Cario, G. ; Figueroa, Maria ; Kalina, T. ; Fiser, K. ; Bourquin, J. P. ; Bornhauser, B. ; Dworzak, M. ; Zuna, J. ; Trka, J. ; Stary, J. ; Hrusak, O. ; Mejstrikova, E. / CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. In: Leukemia. 2014 ; Vol. 28, No. 3. pp. 609-620.
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AU - Reznickova, L.

AU - Van Delft, F. W.

AU - Vodickova, E.

AU - Volejnikova, J.

AU - Zemanova, Z.

AU - Polgarova, K.

AU - Cario, G.

AU - Figueroa, Maria

AU - Kalina, T.

AU - Fiser, K.

AU - Bourquin, J. P.

AU - Bornhauser, B.

AU - Dworzak, M.

AU - Zuna, J.

AU - Trka, J.

AU - Stary, J.

AU - Hrusak, O.

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