Aberrant expression of microRNA in polycythemia vera.
BACKGROUND
Polycythemia vera is a clonal hematopoietic stem cell disorder in which the JAK2 V617F mutation is observed in >95% of patients, but an as yet unidentified process appears to initiate the clonal expansion of hematopoiesis. Because microRNA regulate hematopoietic differentiation, we hypothesized that dysregulated expression of microRNA may contribute to the pathophysiology of polycythemia vera.


METHODS
We performed gene expression profiling in five patients with polycythemia vera and in five controls using CombiMatrix MicroRNA CustomArray. ANOVA identified deregulated microRNA in polycythemia vera, and their expression was studied in a larger set of samples by quantitative reverse transcriptase polymerase chain reaction. The expression of these microRNA was also analyzed in other myeloproliferative disorders.


RESULTS
We observed down-regulation of let-7a and up-regulation of miR-182 in polycythemia vera granulocytes, up-regulation of miR-143, miR-145 and miR-223 in polycythemia vera mononuclear cells, up-regulation of miR-26b in polycythemia vera platelets, and down-regulation of miR-30b, miR-30c and miR-150 in polycythemia vera reticulocytes. JAK2 V617F frequency was positively correlated with miR-143 expression and inversely correlated with let-7a, miR-30c, miR-342 and miR-150. Transcript level of predicted target genes was determined, and overexpression of IRAK2 was detected in all granulocytes from patients with myeloproliferative disorders and in polycythemia vera reticulocytes. Abnormally high HMGA2 microRNA was found in myelofibrosis granulocytes.


CONCLUSIONS
Our study demonstrates that peripheral blood cells from patients with polycythemia vera have microRNA signatures distinct from those of controls. Our findings of aberrant microRNA expression underline the complexity of the molecular basis of polycythemia vera.
University of Utah, School of Medicine, Hematology Division, Salt Lake City, Utah 84132, USA.
Hana
H
Bruchova
Michaela
M
Merkerova
Josef T
JT
Prchal
D002454:Cell Differentiation; D019070:Cell Lineage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D035683:MicroRNAs / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011087:Polycythemia Vera / Q000235:genetics* / Q000378:metabolism*; D055728:Primary Myelofibrosis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; C507924:JAK2 protein, human; D053614:Janus Kinase 2