title: CD49d (ITGA4) expression is a predictor of time to first treatment in patients with chronic lymphocytic leukaemia and mutated IGHV status.
abstract: We investigated CD49d (also termed ITGA4) expression and its biological and clinical correlations in 415 patients with chronic lymphocytic leukaemia. CD49d expression was stable over the course of the disease. A high expression of CD49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or β2 -microglobulin levels; all p < 0·05) and aggressive disease biology (increased ZAP70 or CD38, unmutated IGHV, trisomy 12, mutations of NOTCH1 and SF3B1; all P < 0·05). A higher CD49d expression was also associated with a lower blood lymphocyte count and a higher number of lymphoid areas involved by the disease. Patients with high CD49d expression were treated more frequently (55% vs. 27%; P < 0·001) and earlier (median time to treatment [TTT] 65·4 months vs. not reached; P < 0·001) than those with low CD49d expression. However, no significant differences in response rates were observed. In the subgroup of patients with mutated IGHV, high CD49d expression was predictive of a shorter TTT while other markers, such as ZAP70 and CD38, were not. In conclusion, in this study CD49d expression correlated with high-risk CLL biomarkers and proved to be useful for separating patients with mutated IGHV into two different prognostic groups.
authors.affiliation: Department of Haematology, Institute of Haematology and Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.|Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Tycho
authors.initials: T
authors.lastname: Baumann
authors.affiliation: Department of Haematology, Institute of Haematology and Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Department of Haematology, Institute of Haematology and Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Santacruz
authors.affiliation: Department of Haematology, Institute of Haematology and Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.|Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez-Trillos
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rozman
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.|Institute for Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: López
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Carrió
authors.affiliation: Haematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.affiliation: Department of Haematology, Institute of Haematology and Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D039441:Integrin alpha4 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D039441:Integrin alpha4
keywords: CD49d; IGHV; chronic lymphocytic leukaemia; flow cytometry; prognostic markers