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T-cell leukemia/lymphoma protein 1 (TCL1) was recently shown to display an expression pattern in chronic lymphocytic leukemia (CLL) corresponding to molecular subtypes, where poor-risk patients demonstrated higher expression levels. Here, we examined the mRNA expression pattern of TCL1 in 144 patients with CLL, including 67 immunoglobulin heavy-chain variable (IGHV) mutated, 58 IGHV unmutated and 19 patients with IGHV3-21 usage. A higher TCL1 expression level was detected in patients with CLL with unmutated vs. mutated IGHV genes (P < 0.001), whereas no difference was demonstrated within the IGHV3-21 cohort (i.e., mutated vs. unmutated and stereotyped vs. non-stereotyped complementarity determining region 3). The IGHV3-21 subgroup displayed high TCL1 mRNA expression, differing significantly from other IGHV mutated cases (P < 0.001), although 11/19 had mutated IGHV genes. Furthermore, high TCL1 expression levels were associated with significantly shorter overall survival (P < 0.001). Altogether, we show that TCL1 mRNA expression may predict clinical outcome in CLL and that the IGHV3-21 subset, regardless of mutational status, displays high TCL1 expression.

Trisomy 12 is a frequent abnormality in chronic lymphocytic leukaemia (CLL). The biological importance of trisomy 12 is still poorly understood but it has been suggested that one or several genes are duplicated leading to malignant transformation. We present a case with amplification of 12q13-22 found in a clinically aggressive relapse of CLL. A smaller region, 12q13-15, was amplified most frequently and a YAC containing the MDM2 gene gave the highest number of signals. Additionally, in a subclone an amplicon containing at least 5 copies of a cosmid from 12q23-24 was detected. The case shows that small duplications of chromosome 12, not revealed by cytogenetic analysis, may occur in CLL. Also, it shows that cytogenetic clonal evolution can occur in CLL without morphological evidence of blast transformation. Our results indicate that the 12q13-15 region carries an important gene for CLL progression.