title: IgM peak independently predicts treatment-free survival in chronic lymphocytic leukemia and correlates with accumulation of adverse oncogenetic events.
abstract: We examined the significance of IgM peaks in chronic lymphocytic leukemia (CLL), including its association with newly reported MYD88, BIRC3, NOTCH1 and SF3B1 mutations. A total of 27, 25, 41 and 57 patients with monoclonal IgM or IgG peaks (IgM and IgG groups), hypogammaglobulinemia (Hypo-γ group) and normal immunoglobulin serum levels (normal-γ group) were, respectively, included. IgM peaks were mainly associated with Binet stage C and the del(17p). Biased usage of IGHV3-48 was shared by both IgM and IgG groups. IGHV3-74 and IGHV4-39 gene rearrangements were specific for IgM and IgG peaks, respectively. SF3B1, NOTCH1, MYD88 and BIRC3 mutation frequencies were 12%, 4%, 2% and 2%, respectively, being over-represented in IgM, IgG and Hypo-γ groups for SF3B1, and being equal between normal-γ and IgM groups for MYD88. Overall, 76%, 87%, 49% and 42% of cases from IgM, IgG, Hypo-γ and normal-γ groups had at least one intermediate or poor prognosis genetic marker, respectively. By multivariate analysis, IgM peaks were associated with shorter treatment-free survival independently from any other univariate poor prognosis biological parameters, including IgG peaks, Hypo-γ, IGHV status, SF3B1 mutations, cytogenetics and lymphocytosis. Therefore, as with IgG peaks, IgM peaks aggravated the natural course of CLL, with increased accumulation of adverse genetic events.
authors.affiliation: 1] Laboratory of Hematology, University Hospital Dupuytren, Limoges, France [2] UMR CNRS 7276, Faculty of Medicine, Limoges, France.
authors.forename: D
authors.initials: D
authors.lastname: Rizzo
authors.affiliation: 1] Laboratory of Hematology, University Hospital Dupuytren, Limoges, France [2] UMR CNRS 7276, Faculty of Medicine, Limoges, France.
authors.forename: J
authors.initials: J
authors.lastname: Chauzeix
authors.affiliation: Laboratory of Hematology, University Hospital Dupuytren, Limoges, France.
authors.forename: F
authors.initials: F
authors.lastname: Trimoreau
authors.affiliation: UMR INSERM S-850, Faculty of Medicine, Limoges, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Woillard
authors.affiliation: Laboratory of Hematology, University Hospital, Angers, France.
authors.forename: F
authors.initials: F
authors.lastname: Genevieve
authors.affiliation: Laboratory of Hematology, University Hospital, Angers, France.
authors.forename: A
authors.initials: A
authors.lastname: Bouvier
authors.affiliation: Laboratory of Hematology, University Hospital, Angers, France.
authors.forename: J
authors.initials: J
authors.lastname: Labrousse
authors.affiliation: 1] Laboratory of Immunology and Allergology, University Hospital, Angers, France [2] UMR Inserm 892, CNRS 6299, Faculty of Medicine, Angers, France.
authors.forename: C
authors.initials: C
authors.lastname: Poli
authors.affiliation: Laboratory of Hematology, University Hospital Dupuytren, Limoges, France.
authors.forename: E
authors.initials: E
authors.lastname: Guerin
authors.affiliation: Clinical Hematology and Cellular Therapy, University Hospital Dupuytren, Limoges, France.
authors.forename: N
authors.initials: N
authors.lastname: Dmytruk
authors.affiliation: Clinical Hematology and Cellular Therapy, University Hospital Dupuytren, Limoges, France.
authors.forename: L
authors.initials: L
authors.lastname: Remenieras
authors.affiliation: 1] Laboratory of Hematology, University Hospital Dupuytren, Limoges, France [2] UMR CNRS 7276, Faculty of Medicine, Limoges, France.
authors.forename: J
authors.initials: J
authors.lastname: Feuillard
authors.affiliation: 1] Laboratory of Hematology, University Hospital Dupuytren, Limoges, France [2] UMR CNRS 7276, Faculty of Medicine, Limoges, France.
authors.forename: N
authors.initials: N
authors.lastname: Gachard
mesh_terms: D000368:Aged; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D008218:Lymphocytosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051034:Inhibitor of Apoptosis Proteins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D004247:DNA; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases