CALM-AF10 and HOX11L2 Abnormalities Define Poor Prognostic Subgroups in Pediatric T-Cell Acute Lymphoblastic Leukemia.

Recognition of specific T-ALL subgroups based upon cytogenetic aberrations may have prognostic relevance. The prognostic relevance of recurrent molecular-cytogenetic abnormalities using RQ-PCR and FISH was established for T-ALL patients enrolled on the DCOG protocols, and assigned to SIL-TAL, HOX11, HOX11L2, or CALM-AF10 subgroups or a rest group lacking any of these abnormalities. RQ-PCR data almost completely matched with FISH data. CALM-AF10 was associated with a poor outcome (p=0.005), whereas HOX11L2 and TAL1 subgroups demonstrated a strong trend towards poor and good outcome, respectively. A significant association between HOX11L2 and poor outcome was validated in a second T-ALL cohort comprising 53 pediatric patients that were enrolled on the COALL97 protocol (p=0.01). The TAL1 subgroup was committed to αβ-lineage T-cell developmental stage. HOX11 T-ALLs were all CD1 positive without expression of Cytβ and/or TCR expression reflecting an early cortical developmental stage. The immunophenotype of the HOX11L2 subgroup was rather heterogeneous consisting of samples with TCRγδ expression as well as phenotypic immature cases. Only 41% of HOX11L2 positive cases expressed CD1, indicating that HOX11L2 and HOX11 represent different T-cell developmental stages. CALM-AF10 was associated with a very immature immunophenotype, frequently expressing CD34 and myeloid markers. The TAL1 subgroup was characterized by high expression levels of TAL1, but about half of the samples with no or other aberrations also highly expressed TAL1. LYL1 was highly expressed in the other subgroups, with the highest expression levels in the most immature subgroups. LMO2 gene expression levels closely matched with LYL1 levels. In conclusion, the presence of CALM-AF10 and HOX11L2 abnormalities define poor prognostic subgroups in pediatric T-ALL.