Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

Martha J Glenn; Michael J Madsen; Ethan Davis; Cassandra D Garner; Karen Curtin; Brandt Jones; Justin A Williams; Michael H Tomasson; Nicola J Camp

doi:10.1038/s41408-019-0186-8

Back

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

Journal article

Open access

Peer reviewed

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

Martha J Glenn, Michael J Madsen, Ethan Davis, Cassandra D Garner, Karen Curtin, Brandt Jones, Justin A Williams, Michael H Tomasson and Nicola J Camp

Blood cancer journal (New York), Vol.9(3), pp.25-25

02/26/2019

DOI: 10.1038/s41408-019-0186-8

PMCID: PMC6391432

PMID: 30808891

Files and links (1)

url

https://doi.org/10.1038/s41408-019-0186-8View

Published (Version of record) Open Access

Abstract

Abnormal serum immunoglobulin (Ig) free light chains (FLC) are established biomarkers of early disease in multiple B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL). Heavy chains have also been shown to be biomarkers in plasma cell disorders. An unanswered question is whether these Ig biomarkers are heritable, i.e., influenced by germline factors. CLL is heritable but highly heterogeneous. Heritable biomarkers could elucidate steps of disease pathogenesis that are affected by germline factors, and may help partition heterogeneity and identify genetic pleiotropies across malignancies. Relatives in CLL pedigrees present an opportunity to identify heritable biomarkers. We compared FLCs and heavy chains between relatives in 23 high-risk CLL pedigrees and population controls. Elevated IgM (eIgM) and abnormal FLC (aFLC) ratio was significantly increased in relatives, suggesting that these Ig biomarkers are heritable and could offer risk stratification in pedigree relatives. Within high-risk CLL pedigrees, B-cell lymphoid malignancies were five times more prevalent in close relatives of individuals with eIgM, prostate cancer was three times more prevalent in relatives of individuals with aFLC, and monoclonal B-cell lymphocytosis increased surrounding individuals with normal Ig levels. These different clustering patterns suggest Ig biomarkers have the potential to partition genetic heterogeneity in CLL and provide insight into distinct heritable pleiotropies associated with CLL.

Aged

Aged, 80 and over

B-Lymphocytes - pathology

Biomarkers, Tumor

Case-Control Studies

Early Detection of Cancer

Female

Humans

Immunoglobulin A - blood

Immunoglobulin G - blood

Immunoglobulin Light Chains - blood

Immunoglobulin M - blood

Leukemia, Lymphocytic, Chronic, B-Cell - blood

Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis

Lymphocyte Count

Lymphocytosis

Male

Middle Aged

Pedigree

Phenotype

Prognosis

Details

Title: Subtitle: Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees
Creators: Martha J Glenn - University of Utah
Michael J Madsen - Huntsman Cancer Institute
Ethan Davis - University of Utah
Cassandra D Garner - University of Utah
Karen Curtin - University of Utah
Brandt Jones - Huntsman Cancer Institute
Justin A Williams - Huntsman Cancer Institute
Michael H Tomasson - Roy J. and Lucille A. Carver College of Medicine
Nicola J Camp - Huntsman Cancer Institute
Resource Type: Journal article
Publication Details: Blood cancer journal (New York), Vol.9(3), pp.25-25
DOI: 10.1038/s41408-019-0186-8
PMID: 30808891
PMCID: PMC6391432
NLM abbreviation: Blood Cancer J
ISSN: 2044-5385
eISSN: 2044-5385
Grant note: R01 CA134674 / NCI NIH HHS HHSN261201100016I / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 02/26/2019
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984359936902771

Metrics

15 Record Views

5 Times Cited - Web of Science

See more details