title: Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
abstract: OBJECTIVE
  To investigate the incidence and clinical relevance of classic and new prognostic markers, IGHV gene mutational status, and chromosomal abnormalities in clinical monoclonal B lymphocytosis (cMBL) compared with Rai stage 0 chronic lymphocytic leukemia (Rai0-CLL).
  
  
  METHODS
  A group of 136 patients with cMBL and a group of 216 Rai0-CLL cases were investigated prospectively.
  
  
  RESULTS
  IGHV-mutated cases were significantly more frequent among cMBLs (P = 0.005), whereas the distribution of CD38 and ZAP-70 positive cases, of patients with NOTCH1 and SF3B1 mutations or exhibiting the major CLL cytogenetic abnormalities, was similar in the two groups. Moreover, no significant differences were found either in IGHV/IGHD/IGHJ gene usage or in the overall prevalence of stereotyped IGHV gene sequences. Cells from cMBL and Rai0-CLL exhibited similar gene and microRNA (miRNA) signatures; in addition, when grouped according to the IGHV mutational status, IGHV-unmutated cases showed different transcriptional signatures compared with IGHV-mutated patients, irrespective of the cMBL or Rai0-CLL classification. cMBL diagnosis per se was predictive of longer progression-free survival.
  
  
  CONCLUSIONS
  Our study based on a prospective series of patients indicates that no major differences exist between the circulating cells from cMBL and Rai0-CLL, at least based on a comparison of the markers used in the study. This possibly suggests that the two conditions mainly differ in the initial size of the monoclonal cell population, which may influence the subsequent timing of clonal expansion and clinical manifestations.
authors.affiliation: Authors' Affiliations: Department of Onco-Hematology, A.O. of Cosenza, Cosenza; Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano; SS Molecular Diagnostics, Scientific Direction, and Direzione Scientifica, IRCCS, San Martino IST, Genoa; Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara; Division of Hematology, A.O. Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia; Division of Hematology, University of Messina, Messina; Department of Oncology and Hematology, Pugliese-Ciaccio Hospital; University of Magna Graecia and Cancer Center, Catanzaro; Division of Hematology, Department of Biomedical Sciences, University of Catania and Ferrarotto Hospital, Catania; and Division of Hematology, Department of Clinical and Experimental Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tuana
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Barbara
authors.initials: B
authors.lastname: Zagatti
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Francesco
authors.initials: F
authors.lastname: Maura
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Ernesto
authors.initials: E
authors.lastname: Vigna
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.forename: Carlotta
authors.initials: C
authors.lastname: Massucco
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bossio
authors.forename: Laura
authors.initials: L
authors.lastname: De Stefano
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Sara
authors.initials: S
authors.lastname: Monti
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008218:Lymphocytosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D035683:MicroRNAs; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1