Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia

Xiao Jie Yan, Igor Dozmorov, Wentian Li, Sophia Yancopoulos, Cristina Sison, Michael Centola, Preetesh Jain, Steven L. Allen, Jonathan E. Kolitz, Kanti R. Rai, Nicholas Chiorazzi, Barbara Sherry

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-to-first- treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.

Original languageEnglish (US)
Pages (from-to)5201-5210
Number of pages10
JournalBlood
Volume118
Issue number19
DOIs
StatePublished - Nov 10 2011

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Cytokines
Immunoglobulin Heavy Chains
Survival
Interleukin-15
Mutation
Interleukin-17
Interleukin-5
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Interleukin-1
Interleukin-4
Interleukin-2
Interleukin-6
Therapeutics
Multivariate Analysis
Serum

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Yan, X. J., Dozmorov, I., Li, W., Yancopoulos, S., Sison, C., Centola, M., ... Sherry, B. (2011). Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. Blood, 118(19), 5201-5210. https://doi.org/10.1182/blood-2011-03-342436

Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. / Yan, Xiao Jie; Dozmorov, Igor; Li, Wentian; Yancopoulos, Sophia; Sison, Cristina; Centola, Michael; Jain, Preetesh; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas; Sherry, Barbara.

In: Blood, Vol. 118, No. 19, 10.11.2011, p. 5201-5210.

Research output: Contribution to journalArticle

Yan, XJ, Dozmorov, I, Li, W, Yancopoulos, S, Sison, C, Centola, M, Jain, P, Allen, SL, Kolitz, JE, Rai, KR, Chiorazzi, N & Sherry, B 2011, 'Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia', Blood, vol. 118, no. 19, pp. 5201-5210. https://doi.org/10.1182/blood-2011-03-342436
Yan, Xiao Jie ; Dozmorov, Igor ; Li, Wentian ; Yancopoulos, Sophia ; Sison, Cristina ; Centola, Michael ; Jain, Preetesh ; Allen, Steven L. ; Kolitz, Jonathan E. ; Rai, Kanti R. ; Chiorazzi, Nicholas ; Sherry, Barbara. / Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. In: Blood. 2011 ; Vol. 118, No. 19. pp. 5201-5210.
@article{86acd7b73929445d8355cacbc8352b07,
title = "Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia",
abstract = "Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-to-first- treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.",
author = "Yan, {Xiao Jie} and Igor Dozmorov and Wentian Li and Sophia Yancopoulos and Cristina Sison and Michael Centola and Preetesh Jain and Allen, {Steven L.} and Kolitz, {Jonathan E.} and Rai, {Kanti R.} and Nicholas Chiorazzi and Barbara Sherry",
year = "2011",
month = "11",
day = "10",
doi = "10.1182/blood-2011-03-342436",
language = "English (US)",
volume = "118",
pages = "5201--5210",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

TY - JOUR

T1 - Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia

AU - Yan, Xiao Jie

AU - Dozmorov, Igor

AU - Li, Wentian

AU - Yancopoulos, Sophia

AU - Sison, Cristina

AU - Centola, Michael

AU - Jain, Preetesh

AU - Allen, Steven L.

AU - Kolitz, Jonathan E.

AU - Rai, Kanti R.

AU - Chiorazzi, Nicholas

AU - Sherry, Barbara

PY - 2011/11/10

Y1 - 2011/11/10

N2 - Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-to-first- treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.

AB - Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-to-first- treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.

UR - http://www.scopus.com/inward/record.url?scp=81155133323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81155133323&partnerID=8YFLogxK

U2 - 10.1182/blood-2011-03-342436

DO - 10.1182/blood-2011-03-342436

M3 - Article

VL - 118

SP - 5201

EP - 5210

JO - Blood

JF - Blood

SN - 0006-4971

IS - 19

ER -