Proposal of a genetic classifier for risk group stratification in pediatric T-cell lymphoblastic lymphoma reveals differences from adult T-cell lymphoblastic leukemia

Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities

“…Mutations in the tumour suppressor gene PTEN have been reported in different types of solid and haematological malignancies and were associated with unfavourable outcome of patients. A report of the NHL‐BFM study group identified a significant association of PTEN mutations with adverse outcome of analysed T‐LBL patients (Balbach et al , ). PTEN mutations were detected in 15% of 114 paediatric T‐LBL patients and were associated with a poor pEFS at 5 years of 59 ± 12% compared to 82 ± 4 for PTEN non‐mutated cases ( P = 0·014).…”

“…It is reported that the expression of PTEN was transcriptionally repressed by active NOTCH1 in T‐ALL cell lines, as well as normal mouse thymocytes (Song et al , ; Hales et al , ). This suggests a synergistic effect of both mutations in NOTCH1 and PTEN , but investigation of the prognostic impact of a combination of both genetic markers in the analysed cohort of patients treated according to NHL‐BFM regimens revealed the opposite: the unfavourable prognostic effect of PTEN mutations seems to be abrogated by the favourable prognostic impact of NOTCH1 mutations, as this group of patients presented with a pEFS of 91 ± 9% (Balbach et al , ). Similar associations and interactions of NOTCH1 and PTEN mutations with outcome have recently been described in paediatric T‐ALL treated with BFM‐type regimens (Bandapalli et al , ).…”

Childhood, adolescent and young adult non‐Hodgkin lymphoma: state of the science

“…The most typical cytogenetic abnormalities, especially of the T‐cell immunophenotype commonly include T‐cell receptor (TCR) gene rearrangements, including TRA/TRB (TCRα/β; 14q11‐13), TRB (TCRβ; 7q32‐36) and TRG (TCRγ; 7p15). Other commonly abnormal rearranged genes that have been described include TAL1, TAL2, TCL1, TCL2, TLX1 (previously TCL‐3, HOX‐11), LMO1 (RHOM‐1), LMO2 (RHOM‐2), LYL1, LCK, PBX1 , TCF3 (E2A), NOTCH1 (TAN‐1, NOTCH), FBXW7, PTEN, RAS family , PIK3 family and LOH6q among others (Table ) (Callens et al , ; Bandapalli et al , ; Bonn et al , ; Balbach et al , ). T‐LBL will commonly display early T‐cell gene rearrangements ( TRD [TCRδ], TRG , TRA , and/or TRB ) (Pilozzi et al , ).…”

“…More recently, prognostic factors, such as MDD at diagnosis, LOH6q and genetic mutations of NOTCH1, FBXW7, CASP8AP2 (FLASH) and MIR223 (MiR‐223) among others, have been identified as having an impact on treatment outcome (Coustan‐Smith et al , ; Callens et al , ; Bandapalli et al , ; Bonn et al , ; Balbach et al , ; Michaux et al , ; Pomari et al , ). Balbach et al () proposed a risk classification of paediatric T‐LBL based on NOTCH1, RAS/PIK3 genes , PTEN and LOH6q (Fig ) (Balbach et al , ).…”

Paediatric non‐Hodgkin lymphoma ‐ perspectives in translational biology

“…One recent analysis provided evidence that the mutational status of NOTCH1 / FBXW7 defined a good prognostic subgroup (Callens et al , ). The recently developed score by Balbach et al () defined a good‐risk group (38·5% of patients with a cumulative incidence of relapse of 11 ± 5%, NOTCH1 mutation and no RAS or PIK3–AKT pathway mutation), a high‐risk group (15·4% of patients, NOTCH1 wild type in combination with PTEN mutation and loss of heterozygosityat 6q‐positive patients) and an intermediate‐risk group, which included patients who had neither low‐ nor high‐risk criteria. Despite the fact that the genetically defined risk groups differ slightly between the published studies (Callens et al , ; Balbach et al , ) it seems likely that a genetic definition of risk profiles in T‐LBL will guide the choice of therapy in future trials.…”