title: Stereotyped subset #1 chronic lymphocytic leukemia: a direct link between B-cell receptor structure, function, and patients' prognosis.
abstract: Chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor (BCR) belonging to subset #1 (IGHV1-5-7/ IGKV1-39) display a poor outcome. To characterize their genetic and genomic features and BCR function, we selected 20 subset #1 CLL from a series of 579 cases. Subset #1 CLL, all showing unmutated IGHV, were associated with the presence of del(11q) (50%) in comparison with unmutated CLL, unmutated stereotyped CLL other than subset #1 and with cases using the same IGHV genes but a heterogeneous VH CDR3 (non-subset #1 CLL). There were no distinctive features regarding CD38, ZAP-70, and TP53 disruption. NOTCH1, SF3B1, and BIRC3 were mutated in 15%, 0%, and 5% of cases, respectively, while BIRC3 was deleted in 22% of cases. Microarray unsupervised analysis on 80 unmutated/mutated/stereotyped/non-stereotyped CLL showed a tight clustering of subset #1 cases. Their genomic signature exhibited several differentially expressed transcripts involved in BCR signal transduction, apoptosis regulation, cell proliferation, and oxidative processes, regardless of del(11q). Accordingly, BCR ligation with anti-IgM revealed a significant higher proliferation of subset #1 versus unmutated non-subset #1 CLL, both at baseline and after 24–48 hr stimulation. Subset #1 CLL represent a paradigmatic example of the direct link between BCR structure, function, and patients prognosis.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Simona
authors.initials: S
authors.lastname: Santangelo
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Ilari
authors.forename: Sara
authors.initials: S
authors.lastname: Raponi
authors.forename: Monica
authors.initials: M
authors.lastname: Messina
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.forename: Katia
authors.initials: K
authors.lastname: Bontempi
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell