title: 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.
abstract: Three 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.
authors: j.meijerink@erasmusmc.nl.
authors: Linda
authors: L
authors: Zuurbier
authors: Alejandro
authors: A
authors: Gutierrez
authors: Charles G
authors: CG
authors: Mullighan
authors: Kirsten
authors: K
authors: Canté-Barrett
authors: A Olivier
authors: AO
authors: Gevaert
authors: Johan
authors: J
authors: de Rooi
authors: Yunlei
authors: Y
authors: Li
authors: Willem K
authors: WK
authors: Smits
authors: Jessica G C A M
authors: JG
authors: Buijs-Gladdines
authors: Edwin
authors: E
authors: Sonneveld
authors: A Thomas
authors: AT
authors: Look
authors: Martin
authors: M
authors: Horstmann
authors: Rob
authors: R
authors: Pieters
authors: Jules P P
authors: JP
authors: Meijerink
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D011948:Receptors, Antigen, T-Cell
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