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Pregled bibliografske jedinice broj: 541396

FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis

Desterke, C.; Bilhou-Nabera, C.; Guerton, B.; Martinaud, C.; Tonetti, C.; Clay, D.; Guglielmelli, P.; Vannucchi, A.; Bordessoule, D.; Hasselbalch, H. et al.
FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis // Cancer research (Baltimore), 71 (2011), 8; 2901-2915 doi:10.1158/0008-5472.CAN-10-1731 (međunarodna recenzija, članak, znanstveni)

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Naslov
FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis

Autori
Desterke, C. ; Bilhou-Nabera, C. ; Guerton, B. ; Martinaud, C. ; Tonetti, C. ; Clay, D. ; Guglielmelli, P. ; Vannucchi, A. ; Bordessoule, D. ; Hasselbalch, H. ; Dupriez, B. ; Benzoubir, N. ; Bourgeade, M.F. ; Pierre-Louis, O. ; Lazar, V. ; Vainchenker, W. ; Bennaceur-Griscelli, A. ; Gisslinger, H. ; Giraudier, S. ; Le Bousse-Kerdiles, M.C. ; Bourhis, J.H. ; de Botton, S. ; Briere, J. ; Demory, J.L. ; Fenaux, P. ; Kiladjian, J.J. ; Pasquet, J.M. ; Lippert, E. ; Praloran, V. ; Morel, P. ; Rey, J. ; Roy, L. ; Viallard, J.F. ; Barosi, G. ; Cervantes, F. ; Griesshammer, M. ; , Kreipe, H. ; Kvasnicka, H.M. ; Kušec, Rajko ; Marchetti, M. ; Merup, M. ; Pahl, H. ; Palmblad, J. ; Reilly, J.T. ; Skoda, R. ; Thiele, J.

Izvornik
Cancer research (Baltimore) (0008-5472) 71 (2011), 8; 2901-2915

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
FLT3; p38-MAPK; primary myelofibrosis; cancer

Sažetak
Primary myelofibrosis (PMF) is characterized by increased number of hematopoietic progenitors and a dysmegakaryopoiesis which supports the stromal reaction defining this disease. We showed that increased ligand (FL) levels in plasma, hematopoietic progenitors, and stromal cells from PMF patients were associated with upregulation of the cognate Flt3 receptor on megakaryocytic (MK) cells. This connection prompted us to study a functional role for the FL/Flt3 couple in PMF dysmegakaryopoiesis, as a route to reveal insights into pathobiology and therapy in this disease. Analysis of PMF CD34þ and MK cell transcriptomes revealed deregulation of the mitogen-activated protein kinase (MAPK) pathway along with Flt3 expression. In PMF patients, a higherproportion of circulating Flt3þCD34þCD41þ cells exhibited an increased MAPK effector phosphorylation independently of Jak2V617F mutation. Activation of FL/Flt3 axis in PMF MK cell cultures, in response to FL, induced activation of the p38–MAPK cascade, which is known to be involved in inflammation, also increasing expression of its target genes (NFATC4, p53, AP-1, IL-8). Inhibiting Flt3 or MAPK or especially p38 by chemical, antibody, or silencing strategies restored megakaryopoiesis and reduced phosphorylation of Flt3 and p38 pathway effectors, confirming the involvement of Flt3 in PMF dysmegakaryopoiesis via p38 activation. In addition, in contrast to healthy donors, MKcells derived from PMF CD34þ cells exhibited an FL-induced migration that could be reversed by p38 inhibition. Taken together, our results implicate the FL/Flt3 ligand–receptor complex in PMF dysmegakaryopoiesis through persistent p38–MAPK activation, with implications for therapeutic prospects to correct altered megakaryopoiesis in an inflammatory context.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti



POVEZANOST RADA

Projekti:
108-1980955-3094 - Genetika i funkcija hematopoeze i mikrookoliša Ph- mijeloproliferativnih bolesti (Kušec, Rajko, MZOS ) ( CroRIS)

Ustanove:
Medicinski fakultet, Zagreb

Profili:

Avatar Url Rajko Kušec (autor)

Poveznice na cjeloviti tekst rada:

doi cancerres.aacrjournals.org

Citiraj ovu publikaciju:

Desterke, C.; Bilhou-Nabera, C.; Guerton, B.; Martinaud, C.; Tonetti, C.; Clay, D.; Guglielmelli, P.; Vannucchi, A.; Bordessoule, D.; Hasselbalch, H. et al.
FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis // Cancer research (Baltimore), 71 (2011), 8; 2901-2915 doi:10.1158/0008-5472.CAN-10-1731 (međunarodna recenzija, članak, znanstveni)
Desterke, C., Bilhou-Nabera, C., Guerton, B., Martinaud, C., Tonetti, C., Clay, D., Guglielmelli, P., Vannucchi, A., Bordessoule, D. & Hasselbalch, H. (2011) FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis. Cancer research (Baltimore), 71 (8), 2901-2915 doi:10.1158/0008-5472.CAN-10-1731.
@article{article, author = {Desterke, C. and Bilhou-Nabera, C. and Guerton, B. and Martinaud, C. and Tonetti, C. and Clay, D. and Guglielmelli, P. and Vannucchi, A. and Bordessoule, D. and Hasselbalch, H. and Dupriez, B. and Benzoubir, N. and Bourgeade, M.F. and Pierre-Louis, O. and Lazar, V. and Vainchenker, W. and Bennaceur-Griscelli, A. and Gisslinger, H. and Giraudier, S. and Le Bousse-Kerdiles, M.C. and Bourhis, J.H. and de Botton, S. and Briere, J. and Demory, J.L. and Fenaux, P. and Kiladjian, J.J. and Pasquet, J.M. and Lippert, E. and Praloran, V. and Morel, P. and Rey, J. and Roy, L. and Viallard, J.F. and Barosi, G. and Cervantes, F. and Griesshammer, M. and Kvasnicka, H.M. and Ku\v{s}ec, Rajko and Marchetti, M. and Merup, M. and Pahl, H. and Palmblad, J. and Reilly, J.T. and Skoda, R. and Thiele, J.}, year = {2011}, pages = {2901-2915}, DOI = {10.1158/0008-5472.CAN-10-1731}, keywords = {FLT3, p38-MAPK, primary myelofibrosis, cancer}, journal = {Cancer research (Baltimore)}, doi = {10.1158/0008-5472.CAN-10-1731}, volume = {71}, number = {8}, issn = {0008-5472}, title = {FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis}, keyword = {FLT3, p38-MAPK, primary myelofibrosis, cancer} }
@article{article, author = {Desterke, C. and Bilhou-Nabera, C. and Guerton, B. and Martinaud, C. and Tonetti, C. and Clay, D. and Guglielmelli, P. and Vannucchi, A. and Bordessoule, D. and Hasselbalch, H. and Dupriez, B. and Benzoubir, N. and Bourgeade, M.F. and Pierre-Louis, O. and Lazar, V. and Vainchenker, W. and Bennaceur-Griscelli, A. and Gisslinger, H. and Giraudier, S. and Le Bousse-Kerdiles, M.C. and Bourhis, J.H. and de Botton, S. and Briere, J. and Demory, J.L. and Fenaux, P. and Kiladjian, J.J. and Pasquet, J.M. and Lippert, E. and Praloran, V. and Morel, P. and Rey, J. and Roy, L. and Viallard, J.F. and Barosi, G. and Cervantes, F. and Griesshammer, M. and Kvasnicka, H.M. and Ku\v{s}ec, Rajko and Marchetti, M. and Merup, M. and Pahl, H. and Palmblad, J. and Reilly, J.T. and Skoda, R. and Thiele, J.}, year = {2011}, pages = {2901-2915}, DOI = {10.1158/0008-5472.CAN-10-1731}, keywords = {FLT3, p38-MAPK, primary myelofibrosis, cancer}, journal = {Cancer research (Baltimore)}, doi = {10.1158/0008-5472.CAN-10-1731}, volume = {71}, number = {8}, issn = {0008-5472}, title = {FLT3-mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis}, keyword = {FLT3, p38-MAPK, primary myelofibrosis, cancer} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE

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