Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

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dc.contributor.authorZuurbier, L.
dc.contributor.authorGutierrez, A.
dc.contributor.authorMullighan, C.G.
dc.contributor.authorCante-Barrett, K.
dc.contributor.authorGevaert, A.O.
dc.contributor.authorde Rooi, J.
dc.contributor.authorLi, Y.
dc.contributor.authorSmits, W.K.
dc.contributor.authorBuijs-Gladdines, J.G.
dc.contributor.authorSonneveld, E.
dc.contributor.authorLook, A.T.
dc.contributor.authorHorstmann, M.
dc.contributor.authorPieters, R.
dc.contributor.authorMeijerink, J.P.
dc.date.issued2014
dc.description.abstractThree distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients.
dc.description.statementofresponsibilityLinda Zuurbier, Alejandro Gutierrez, Charles G. Mullighan, Kirsten Canté-Barrett, A. Olivier Gevaert, Johan de Rooi, Yunlei Li, Willem K. Smits, Jessica G.C.A.M. Buijs-Gladdines, Edwin Sonneveld, A. Thomas Look, Martin Horstmann, Rob Pieters, and Jules P.P. Meijerink
dc.identifier.citationHaematologica, 2014; 99(1):94-102
dc.identifier.doi10.3324/haematol.2013.090233
dc.identifier.issn0390-6078
dc.identifier.issn1592-8721
dc.identifier.orcidMullighan, C.G. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/116225
dc.language.isoen
dc.publisherFerrata Storti Foundation
dc.rights©2013 Ferrata Storti Foundation. This is an open-access paper.
dc.source.urihttps://doi.org/10.3324/haematol.2013.090233
dc.subjectPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma
dc.titleImmature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors
dc.typeJournal article
pubs.publication-statusPublished

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