Naslov
Bone marrow renin-angiotensin system expression in polycythaemia vera and essential thrombocythaemia depends on JAK2 mutational status

Autori
Marušić Vrsalović, Maruška ; Pejša, Vlatko ; Štoos Veić, Tajana ; Ostojić Kolonić, Slobodanka ; Ajduković, Radmila ; Hariš, Višnja ; Jakšić, Ozren ; Kušec, Rajko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Leukemia Research, suppl. 2 / John M. Bennett, Terry J. Hamblin - Amsterdam : Elsevier, 2007, 80-80

Skup
Leukemia and Lymphoma, East and West Together

Mjesto i datum
Dubrovnik, Hrvatska, 15.09.2007. - 19.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Bone marrow renin-angiotensin system; polycythaemia vera; essential thrombocythaemia; JAK2

Sažetak
Discovery of V617F mutation in JAK2 tyrosine kinase gene in myeloid progenitors provided new insight into the pathogenesis and clinical understanding of CMPD. There are several lines of evidence suggesting the existence of local hematopoietic bone marrow renin-angiotensin system (RAS) which contributes to the regulation of normal and disturbed hematopoiesis. Recently, it was shown that Jak2 kinase is important upstream component in the regulation of the AGT mRNA transcription: activated Jak2 kinase stimulates AGT gene transcription. These observations suggest possibility for constitutively active, mutated Jak2 to modulate transcriptional activation of AGT gene as well as the expression of other RAS genes in CMPD. Aim: We analyzed the expression of RAS genes (ACE, AGT, AT2R1 and REN) in normal BM and that of PV and ET patients with the respect to the presence of activating V617F JAK2 mutation. Patients and methods: Fourteen PV-JAK2V617Fpos patients (7 male, 7 female, median age 68), thirteen ET-JAKV617Fpos patients (6 male, 7 female, median age 72) and seven ETJAK2V617Fneg patients (3 male, 4 female, median age 66) were included in the study. Samples of normal bone marrow were obtained from fi ve healthy donors. Real-time PCR analysis for ACE, AGT, AT1R1, REN genes and internal housekeeping gene GAPDH was performed using Real Time PCR System. To compensate for inter-PCR variations, normalisation of target genes (ACE, AGT, AT2R1, REN) with an endogenous control (GAPDH) was performed. JAK2 V617F mutational status was determined by the allele-specifi c PCR. Results: ACE expression in BM of PV and ET patients was down-regulated to 2-20% of the donor BM values with no statistically signifi cant difference in expression between patients. AGT expression was signifi cantly higher in PV and in ETJAK2V617Fpos comparing to ET JAK2V617Fneg patients. Renin has shown similar pattern of expression as AGT: it was signifi cantly higher in PV and in ET JAK2V617Fpos patients comparing to ET JAK2V617Fneg patients. AT1R gene was signifi cantly higher expressed in PV patients in comparison to both ET subgroups, JAK2V617F positive or negative patients. ET patients did not differ for AT2R1 expression by their JAK2 mutational status. Conclusion: Our fi ndings indicate up-regulation of AGT, AT2R1 and REN genes and down-regulation of ACE gene expression in clonal hematopoiesis of PV and ET. Different expression pattern of major RAS components in BM of PV and ET compared to normal BM is clearly related to the existence of JAK2V617F mutation and less to the PV or ET disease phenotype. However, interesting exception is excessive expression of AT2R1 in PV that was not observed in ET irrespective of JAK2 mutation. This latest observation provides ground for the future experimental and clinical studies for the use of AT2R1 blockers in improving clinical management of JAK2V617Fpos PV.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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