PMID- 21300928
OWN - NLM
STAT- MEDLINE
DCOM- 20110527
LR  - 20220318
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 10
DP  - 2011 Apr 1
TI  - Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently 
      prognostic in primary myelofibrosis: a comprehensive cytokine profiling study.
PG  - 1356-63
LID - 10.1200/JCO.2010.32.9490 [doi]
AB  - PURPOSE: Abnormal cytokine expression accompanies myelofibrosis and might be a 
      therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study 
      describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis 
      (PMF) and examines their phenotypic correlates and prognostic significance. 
      PATIENTS AND METHODS: Patients included in this study were required to have 
      archived plasma, bone marrow biopsy, and cytogenetic information available at the 
      time of first referral to the Mayo Clinic. Multiplex biometric sandwich 
      immunoassay was used to measure plasma levels of 30 cytokines. RESULTS: In total, 
      127 PMF patients were studied; comparison with normal controls (n = 35) revealed 
      significantly increased interleukin-1beta (IL-1beta), IL-1RA, IL-2R, IL-6, IL-8, IL-10, 
      IL-12, IL-13, IL-15, tumor necrosis factor alpha (TNF-alpha), granulocyte 
      colony-stimulating factor (G-CSF), interferon alfa (IFN-alpha), macrophage 
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, hepatocyte growth factor (HGF), 
      IFN-gamma-inducible protein 10 (IP-10), monokine induced by IFN-gamma (MIG), monocyte 
      chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) 
      levels and decreased IFN-gamma levels. In treatment-naive patients (n = 90), 
      increased levels of IL-8 (P < .001), IL-2R (P < .001), IL-12 (P < .001), IL-15 (P 
      = .001), and IP-10 (P = .003) were independently predictive of inferior survival. 
      A similar multivariable analysis that included all 127 study patients confirmed 
      the prognostic value of these five cytokines, and IL-8, IL-2R, IL-12, and IL-15 
      remained significant when risk stratification, according to the recently revised 
      Dynamic International Prognostic Scoring System (DIPSS plus), was added to the 
      multivariable model. Leukemia-free survival was predicted by IL-8, which was also 
      the only cytokine associated with >/= 1% circulating blasts. Other 
      cytokine-phenotype associations included increased IL-8 and constitutional 
      symptoms; IL-2R, IL-12, and transfusion need; IL-2R, IL-8, and leukocytosis; 
      IP-10 and thrombocytopenia; HGF, MIG, IL-1RA, and marked splenomegaly; and 
      IL-1RA, IL-2R, IP-10, MIP-1beta, and JAK2V617F. A two-cytokine (IL-8/IL-2R) -based 
      risk categorization delineated prognostically different groups within specific 
      DIPSS plus risk categories. CONCLUSION: This study signifies the presence of 
      specific cytokine-phenotype associations in PMF and a prognostically relevant 
      plasma cytokine signature that might prove useful as a laboratory tool for 
      predicting and monitoring treatment response.
FAU - Tefferi, Ayalew
AU  - Tefferi A
AD  - Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
FAU - Vaidya, Rakhee
AU  - Vaidya R
FAU - Caramazza, Domenica
AU  - Caramazza D
FAU - Finke, Christy
AU  - Finke C
FAU - Lasho, Terra
AU  - Lasho T
FAU - Pardanani, Animesh
AU  - Pardanani A
LA  - eng
PT  - Journal Article
DEP - 20110207
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Interleukin-15)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Interleukin-2)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*blood
MH  - Biopsy
MH  - Bone Marrow Examination
MH  - Case-Control Studies
MH  - Chi-Square Distribution
MH  - Cytogenetic Analysis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Interleukin-12/*blood
MH  - Interleukin-15/*blood
MH  - Interleukin-8/*blood
MH  - Janus Kinase 2/genetics
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Minnesota
MH  - Mutation
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Primary Myelofibrosis/blood/genetics/*immunology/pathology
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - *Protein Array Analysis/methods
MH  - Receptors, Interleukin-2/*blood
MH  - Risk Assessment
MH  - Risk Factors
MH  - Up-Regulation
EDAT- 2011/02/09 06:00
MHDA- 2011/05/28 06:00
CRDT- 2011/02/09 06:00
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/05/28 06:00 [medline]
AID - JCO.2010.32.9490 [pii]
AID - 10.1200/JCO.2010.32.9490 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Apr 1;29(10):1356-63. doi: 10.1200/JCO.2010.32.9490. Epub 2011 
      Feb 7.