title: IGHV3-21 gene usage is associated with high TCL1 expression in chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Dept of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. mahmoud.mansouri@genpat.uu.se
authors.forename: Mahmoud R
authors.initials: MR
authors.lastname: Mansouri
authors.forename: Marie
authors.initials: M
authors.lastname: Sevov
authors.forename: Anna
authors.initials: A
authors.lastname: Aleskog
authors.forename: Mikael
authors.initials: M
authors.lastname: Jondal
authors.forename: Mats
authors.initials: M
authors.lastname: Merup
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C090851:TCL1A protein, human