SIL-TAL1fusion gene negative impact in T-cell acute lymphoblastic leukemia outcome

Abstract

SIL-TAL1 fusion gene and the ectopic expression of HOX11L2 are common molecular abnormalities in T-cell acute lymphoblastic leukemia (T-ALL). To verify their influence on outcome, we analyzed a Brazilian pediatric T-ALL series of cases. One hundred and ninety two children, age ranged 0-21 years old, were consecutively diagnosed and treated. Reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to identify the molecular alterations. Kaplan-Meyer method was applied to estimate overall survival. The most frequent maturation stage was T-IV (40.1%), and 30.7% of cases were CD10(+). SIL-TAL1(+) and HOX11L2(+) accounted for 26.7% and 10.3% of the cases, respectively. The overall survival (OS) was 74% in 80-month follow-up. HOX11L2(+) was not predictive factor for outcome. Considering patients younger than nine years-old, those with SIL-TAL1(+) presented a poorer outcome (p = 0.02). The results of this study suggest that in the Brazilian population only the presence of SIL-TAL1 can predict outcome in a restricted group of patients.

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

“…Subjects were ascertained from four geographical regions assembled by a national network of acute leukaemia studies [12] and the majority of cases were included in a previous publication [6]. The exclusion criteria applied for the analysis was age (12 months) and the diagnosis of T-lymphoblastic lymphoma according to WHO classification [13,14].…”

“…After mononuclear cell separation using Ficoll-Hypaque-Hystopaque ® , immunophenotype was performed in blast cells by flow cytometry using a defined panel of monoclonal antibodies, as previously described [6] and/or by immunohistochemistry methods [13,14]. Immunological classification of T-ALL was based on criteria previously published by the European Group for the Immunological Characterization of Leukaemias [18].…”

“…cDNA was generated by reverse transcription of 2 μg of total RNA using First-Strand cDNA Synthesis Kit™ (Amersham Biosciences UK Limited, Little Chalfont, UK), and stored at −20°C. The integrity of cDNA was examined by amplifying a fragment of the GAPDH constitutive gene, according to reported conditions [6]. …”

“…T-ALL is also characterized by the occurrence of multiple genetic alterations that result in the transformation of T-cell precursors. Distinct immunophenotypic subsets and somatic genetic alterations have been occasionally correlated with prognosis, but these results could not be consistently replicated by other studies, requiring larger number of cases to confirm associations that could support an improvement in treatment [3-6]. …”

The impact of immunological and biomolecular investigations on the outcome of children with acute lymphoblastic leukemia - experience of IIIrd Paediatric Clinic Timisoara

“…Patients exhibiting the E2A-PBX1 gene fusion, presented late relapses, after more than 3 years after the diagnosis. Different studies showed controversial results with respect to the prognosis of the patients SIL-TAL rearrangements (30)(31)(32). In the present study, early relapses after diagnosis were registered for the patients having SIL-TAL rearrangements: one patient presented relapse in less than one year from the diagnosis, the other two patients relapsed between one year and two years after the moment of diagnosis.…”