title: CD49d associates with nodal presentation and subsequent development of lymphadenopathy in patients with chronic lymphocytic leukaemia.
abstract: CD49d is a surface integrin that is expressed on chronic lymphocytic leukaemia (CLL) cells, and strongly correlates with more aggressive disease. Given its association with cell-cell adhesion and leucocyte trafficking, we hypothesized that patients with high CD49d expression would experience a clinical course dominated by lymphadenopathy. CD49d expression was measured by flow cytometry and considered positive if expressed by ≥30% of CLL cells. The study included 797 newly diagnosed CLL/small lymphocytic leukaemia patients; 279 (35%) were CD49d positive. CD49d-positive patients were more likely to present with lymphadenopathy (P < 0·001); a finding that persisted after adjusting for fluorescence in situ hybridisation (FISH) and IGHV mutation status [odds ratio (OR) 2·51; 95% confidence interval (CI) 1·64-3·83; P < 0·001]. Among CLL Rai 0 patients, CD49d positivity was associated with shorter time to development of lymphadenopathy (3·2 years vs not reached, P < 0·01). This association was maintained after adjusting for either FISH [hazard ratio (HR) 2·18; 95% CI 1·25-3·81; P = 0·006) or IGHV status (HR 2·02; 95% CI 1·11-3·69; P = 0·02) individually, but was attenuated when adjusting by both (HR 1·72; 95% CI 0·88-3·38; P = 0·11).These data demonstrate that CD49d-positive CLL patients experience a disease course dominated by lymphadenopathy. These findings could have implications for therapy selection and disease monitoring.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Paolo
authors.identifier: 0000-0002-7445-1459
authors.initials: P
authors.lastname: Strati
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Parikh
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Kari G
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Achenbach
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D039441:Integrin alpha4 / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000072281:Lymphadenopathy / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007135:Immunoglobulin Variable Region; D039441:Integrin alpha4
keywords: CD49d; chronic lymphocytic leukaemia; lymphadenopathy; small lymphocytic lymphoma