title: Gene Expression and Serum Cytokine Profiling of Low Stage CLL Identify WNT/PCP, Flt-3L/Flt-3 and CXCL9/CXCR3 as Regulators of Cell Proliferation, Survival and Migration.
abstract: Gene expression profiling (GEP) of 8 stage 0/I untreated Chronic Lymphocytic Leukemia (CLL) patients showed over-expression of Frizzled 3 (FZD3)/ROR-1 receptor tyrosine kinase (RTK), FLT-3 RTK and CXCR3 G-protein coupled receptor (GPCR). RT-PCR of 24 genes in 21 patients of the WNT pathway corroborated the GEP. Transforming growth factorβ, fibromodulin, TGFβRIII and SMAD2 are also over-expressed by GEP. Serum cytokine profiling of 26 low stage patients showed elevation of IFNγ, CSF3, Flt-3L and insulin-like growth factor binding protein 4. In order to ascertain why CLL cells grow poorly in culture, a GEP of 4 CLL patients cells at 0 hr and 24 hr in culture demonstrated over expression of CXCL5, CCL2 and CXCL3, that may recruit immune cells for survival. Treatment with thalidomide, an immunomodulatory agent, showed elevation of CCL5 by GEP but was not cytotoxic to CLL cells. Our data suggest an interplay of several oncogenic pathways, cytokines and immune cells that promote a survival program in CLL.
authors.affiliation: Department of Hematology/Oncology, Arizona Cancer Center, Tucson, AZ 85724, USA.
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.forename: James
authors.initials: J
authors.lastname: Choi
authors.forename: Laurence
authors.initials: L
authors.lastname: Cooke
authors.forename: Bram
authors.initials: B
authors.lastname: Simons
authors.forename: Christopher
authors.initials: C
authors.lastname: Riley
authors.forename: Thomas
authors.initials: T
authors.lastname: Klinkhammer
authors.forename: Rohit
authors.initials: R
authors.lastname: Sud
authors.forename: Sirisha
authors.initials: S
authors.lastname: Maddipoti
authors.forename: Sean
authors.initials: S
authors.lastname: Hehn
authors.forename: Harinder
authors.initials: H
authors.lastname: Garewal
authors.forename: Catherine
authors.initials: C
authors.lastname: Spier