T-ALLs Prognostic and oncogenic relevance of TLX1/HOX11 expression level in

Abstract: TLX1 is a homeodomain transcription factor generally associated with a favourable outcome in T-ALL. However, the molecular mechanisms of TLX1 deregulation remain unclear and various transcript levels in the absence of 10q24 abnormalities have been reported. A reproducible and accurate delineation of TLX1+ T-ALL will be necessary for proper therapeutic stratification. We have studied 264 unselected T-ALLs (171 adults and 93 children) and show that T-ALLs expressing high levels of TLX1 (n=35, 13%), defined as a RQ-PCR ratio of TLX1 >1.00E+00 ABL , form a homogeneous oncogenic group, based on their uniform stage of maturation arrest and oncogenetic and transcriptional profiles. Furthermore, TLX1-high T-ALLs harbour molecular TLX1 locus abnormalities in the vast majority (31/33), a proportion largely underestimated by standard karyotypic screening. T-ALLs expressing TLX1 at lower levels (n=57, 22%) do not share these characteristics. Prognostic analysis within the adult LALA94 and GRAALL03 prospective protocols demonstrate a better event-free (p=0,035) and a marked trend for longer overall survival (p=0,059) for TLX1-high T-ALLs, while the expression of lower levels of

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