Transcriptional Profiling Of Polycythemia Vera Identifies Gene Expression Patterns Both Dependent And Independent From The Action Of JAK2V617F
Articolo
Data di Pubblicazione:
2010
Abstract:
Purpose: To understand the changes in gene expression in PV progenitor cells and
their relationship to JAK2V617F Experimental Design: mRNA isolated from CD34+
cells from 9 PV patients and normal controls was profiled using Affymetrix arrays. Gene
expression change mediated by JAK2V617F was determined by profiling CD34+ cells
transduced with the kinase and by analysis of leukemia cell lines harboring JAK2V617F,
treated with an inhibitor. Results: A PV expression signature was enriched for genes
involved in hematopoietic development, inflammatory responses and cell proliferation.
By quantitative RT-PCR, 23 genes were consistently deregulated in all patient samples.
Several of these genes such as WT1 and KLF4 were regulated by JAK2, while others
such as NFIB and EVI1 appeared to be deregulated in PV by a JAK2 independent
mechanism. Using cell line models and comparing gene expression profiles of cell lines
and PV CD34+ PV specimens, we have identified panels of JAK2 dependent 14 genes
and JAK2 independent 12 genes. These two 14 and 12 gene sets could separate not
only PV from normal CD34+ specimens, but also other MPN such as ET and MF from
their normal counterparts. Conclusions: A subset of the aberrant gene expression in
PV progenitor cells can be attributed to the action of the mutant kinase, but there remain
a significant number of genes characteristic of the disease but deregulated by as yet
unknown mechanisms. Genes deregulated in PV as a result of the action of
JAK2V617F or independent of the kinase may represent other targets for therapy
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
Berkofsky-Fessler W; Buzzai M; Kim MK; Fruchtman S; Najfeld V; Min DJ; Costa FF; Bischoff JM; Soares MB; McConnell MJ; Zhang W; Levine R; Gilliland DG; Calogero R; Licht JD
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