title: Genetic and cytokine changes associated with symptomatic stages of CLL.
abstract: The pathogenesis and drug resistance of symptomatic CLL patients involves genetic changes associated with the CLL clone as well as changes within the microenvironment. To further understand these processes, we compared early stage CLL to symptomatic late stage using gene expression and serum cytokine profiling to gain insight of the genetic and microenvironment changes associated with the most severe form of the disease. Patients were classified into low stage (Rai stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were obtained on pretreatment samples using the HG-U133A 2.0 Affymetrix platform. A comparison of low versus high stage CLL revealed a set of 21 genes differentially expressed genes. 15 genes were up regulated in the high stage compared to low stage while 6 genes were down regulated. Analysis of GO molecular function revealed 9 of 21 genes were involved in transcription factor activity. Serum cytokine profiles showed six cytokines to be significantly different in high stage patients. Two chemokines, SDF-1/CXCL12 and uPAR known to be involved in stem cell mobilization and homing were increased in serum of high stage patients. This study has identified therapeutic targets for symptomatic CLL patients.
authors: University of Arizona, United States. Electronic address: aagarwal@uacc.arizona.edu.
authors: Amit
authors: A
authors: Agarwal
authors: University of Tennessee, United States.
authors: Lawrence
authors: L
authors: Cooke
authors: University of Arizona, United States.
authors: Christopher
authors: C
authors: Riley
authors: University of Tennessee, United States.
authors: Wenqing
authors: W
authors: Qi
authors: University of Arizona, United States.
authors: David
authors: D
authors: Mount
authors: University of Tennessee, West Clinic, United States.
authors: Daruka
authors: D
authors: Mahadevan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D059467:Transcriptome
chemical_list: D016207:Cytokines
keywords: CSNK1E; Chronic lymphocytic leukemia; Cytokine profile; Gene expression profile; SDF-1/CXCL12; SETD8; Stage progression; Transcription factors