Dataset Information

Chromosomal aberrations in peripheral blood lymphocytes and risk for non-Hodgkin lymphoma.

ABSTRACT: Chromosomal aberrations (CAs) are thought to be integrative biomarkers that reflect exposure to chromosome-damaging carcinogens and host factors. To investigate whether CAs indicate non-Hodgkin lymphoma (NHL) risk, we evaluated 200 metaphase spreads each for 67 incident low-grade, untreated NHL cases and 57 controls matched on age, sex, and storage time of cryopreserved lymphocytes. Hyperdiploidy of 47 chromosomes was statistically significantly associated with increased NHL risk with odds ratios of 1.4 (97% confidence interval [CI] = 0.6-3.5) and 3.5 (95% CI = 1.1-10.9) for medium and high levels of hyperdiploidy, respectively, compared to the lowest level (P-trend = .04). Hypodiploidy of 43 and 44 chromosomes increased NHL risk 3.3-fold (95% CI = 1.2-8.7) and 2.2 (95% CI = 1.0-5.2), respectively, compared to those without the event; total hypodiploidy was only moderately associated with risk. Chromosome and chromatid breaks were not associated with NHL risk. Our data suggest for the first time that aneuploidy identified in cultured, peripheral lymphocytes may be potential indicators of NHL risk.

SUBMITTER: Wang SS

PROVIDER: S-EPMC6284247 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Chromosomal aberrations in peripheral blood lymphocytes and risk for non-Hodgkin lymphoma.

Wang Sophia S SS Davis Scott S Hartge Patricia P Cozen Wendy W Severson Richard K RK Cerhan James R JR Rothman Nathaniel N

Journal of the National Cancer Institute. Monographs 20080101 39

Chromosomal aberrations (CAs) are thought to be integrative biomarkers that reflect exposure to chromosome-damaging carcinogens and host factors. To investigate whether CAs indicate non-Hodgkin lymphoma (NHL) risk, we evaluated 200 metaphase spreads each for 67 incident low-grade, untreated NHL cases and 57 controls matched on age, sex, and storage time of cryopreserved lymphocytes. Hyperdiploidy of 47 chromosomes was statistically significantly associated with increased NHL risk with odds ratio ...[more]

PMID: 18648009

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Project description:Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear.The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated.CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02-70.92) vs 0.42 (0.04-2.97), p < 0.0001. Their percentage remained significantly higher even considering HL (n = 31), indolent (n = 31) and aggressive (n = 62) B-cell NHL patients separately: 1.54 (0.28-26.34), 2.15 (0.02-20.08), and 2.96 (0.25-70.92), respectively, p < 0.0001. CD66b+CD33dimHLA-DR-cells in patient PBMCs were mostly composed of mature CD11b+CD16+ low-density neutrophils in an activated status, as revealed by their higher CD11b and CD66b expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR- G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression.PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR- G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions.

Dataset Information

Chromosomal aberrations in peripheral blood lymphocytes and risk for non-Hodgkin lymphoma.

Publications

Chromosomal aberrations in peripheral blood lymphocytes and risk for non-Hodgkin lymphoma.

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