title: Clinical significance of LAIR1 (CD305) as assessed by flow cytometry in a prospective series of patients with chronic lymphocytic leukemia.
abstract: Most patients affected by chronic lymphocytic leukemia are diagnosed by flow cytometry. Several immunophenotypic markers have been identified as significant and independent prognostic variables, especially from retrospective cohorts. However, while attractive because their detection is inexpensive and feasible in most laboratories, only few have been validated by independent series. The expression of leukocyte-associated immunoglobulin-like receptor-1 (also known as LAIR1, LAIR-1 or CD305), an inhibitor of B-cell receptor-mediated signaling, has been reported to be lacking in high-risk chronic lymphocytic leukemia. However, its correlation with biological variables and its prognostic significance remain unknown. We investigated 311 consecutive patients, prospectively enrolled since 2007. Methods for studying patients were standardized and included clinical assessment, immunophenotype, fluorescence in situ hybridization, and status of immunoglobulin heavy chain variable region genes. Overall, 22.1% of patients had Binet stage B or C disease, 38.5% had unmutated immunoglobulin genes, 15.1% had high-risk cytogenetic abnormalities, 23.4% were CD38(+), 37.8% CD49d(+), and 59.8% LAIR1(+). Expression of LAIR1 was inversely related to that of CD38 (P=0.0005), but was not associated with CD49d expression (P=0.96). A significantly lower expression of LAIR1 was observed in patients with Binet stage B or C disease (P=0.023), and in the presence of high-risk cytogenetic abnormalities (P=0.048) or unmutated immunoglobulin heavy chain variable region genes (P<0.0001). At univariate analysis LAIR1(+) was significantly associated with longer time to first treatment (P=0.0002). This favorable effect of LAIR1(+) was confirmed by multivariate analysis (hazard ratio=2.1, P=0.03 for LAIR1). Our results indicate that LAIR1 expression is a reliable and inexpensive marker capable of independently predicting time to first treatment in newly diagnosed unselected patients with chronic lymphocytic leukemia.
authors.affiliation: carlovisco@hotmail.com.
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.forename: Erika
authors.initials: E
authors.lastname: Falisi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giaretta
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscaro
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Novella
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Stefania
authors.initials: S
authors.lastname: Fortuna
authors.forename: Silvia
authors.initials: S
authors.lastname: Finotto
authors.forename: Eliana
authors.initials: E
authors.lastname: Amati
authors.forename: Francesco
authors.initials: F
authors.lastname: Maniscalco
authors.forename: Anna
authors.initials: A
authors.lastname: Montaldi
authors.forename: Alberta
authors.initials: A
authors.lastname: Alghisi
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Aprili
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaldi
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
authors.forename: Achille
authors.initials: A
authors.lastname: Ambrosetti
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
chemical_list: D007143:Immunoglobulin Heavy Chains; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1