Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia.
The role of circulating cytokines and chemokines (C&Ckine) in activating signal transduction in leukemic cells is incompletely defined. We hypothesized that comprehensive profiling of C&Ckine expression in leukemia would provide greater insight compared with individual analyses. We used multiplex array technology to simultaneously measure the level of 27 C&Ckines in serum from 176 acute myelogenous leukemia (AML) and 114 myelodysplastic syndrome (MDS) patients and 19 normal controls. C&Ckine levels in AML and MDS differed significantly from normal controls (5 higher, 13 lower) but were similar to each other for 24 of 27 analytes, with interleukin-8 and interleukin-13 higher in AML and vascular endothelial growth factor A higher in MDS. Levels did not correlate with age, gender, infection, or blood counts; however, 3 correlated with specific cytognetic abnormalities in AML. Individually, few cytokines had any correlation with response or survival. In newly diagnosed AML, 8 C&Ckine signatures, distinct from the normal control signature, were observed. These signatures had prognostic impact, affecting remission, primary resistance, relapse rates, and overall survival, individually (P = .003) and in multivariable analysis (P = .004). These patterns suggest specific therapeutic interventions to investigate in subsets of AML patients. In conclusion, C&Ckine expression in AML and MDS differs from normal, is similar with one another, and forms recurrent patterns of expression with prognostic relevance.
Kornblau
Steven M
SM
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. skornblau@mdanderson.org
McCue
David
D
Singh
Neera
N
Chen
Wenjing
W
Estrov
Zeev
Z
Coombes
Kevin R
KR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000097:blood*; D016000:Cluster Analysis; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D025341:Principal Component Analysis; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D018925:Chemokines