Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia

被引：169

作者：

Vannucchi, Alessandro M. ^{[1
,2
]}

Antonioli, Elisabetta ^{[1
,2
]}

Guglielmelli, Paola ^{[1
,2
]}

Pancrazzi, Alessandro ^{[1
,2
]}

Guerini, Vittoria ^{[3
]}

Barosi, Giovanni ^{[4
]}

Ruggeri, Marco ^{[5
,6
]}

Specchia, Giorgina ^{[7
]}

Lo-Coco, Francesco ^{[8
]}

Delaini, Federica ^{[3
]}

Villani, Laura ^{[4
]}

Finotto, Silvia ^{[5
,6
]}

Ammatuna, Emanuele ^{[8
]}

Alterini, Renato ^{[1
,2
]}

Carrai, Valentina ^{[1
,2
]}

Capaccioli, Gloria ^{[1
,2
]}

Di Lollo, Simonetta ^{[9
]}

Liso, Vincenzo ^{[7
]}

Rambaldi, Alessandro ^{[3
]}

Bosi, Alberto ^{[1
,2
]}

Barbui, Tiziano ^{[3
]}

机构：

[1] Univ Florence, Dipartimento Area Crit Medicochirurg, UF Ematol, I-50134 Florence, Italy

[2] Ist Toscano Tumori, Florence, Italy

[3] Osped Riuniti Bergamo, Div Ematol, I-24100 Bergamo, Italy

[4] Policlin San Matteo, IRCCS, Fdn Ist Ricovero & Cura Carattere Sci, Lab Epidemiol Clin, I-27100 Pavia, Italy

[5] Osped San Bortolo, Dipartimento Ematol, Vicenza, Italy

[6] Osped San Bortolo, Ctr Emofilia & Trombosi, Vicenza, Italy

[7] Univ Bari, Dipartimento Ematol, Bari, Italy

[8] Univ Roma Tor Vergata, Dipartimento Biopatol & Diagnost Immagini, Rome, Italy

[9] Univ Florence, Dipartimento Oncol, Florence, Italy

来源：

BLOOD | 2008年 / 112卷 / 03期

关键词：

D O I：

10.1182/blood-2008-01-135897

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515UK mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671 F mutation. MPLW515UK patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwV JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factorformicrovesseldisturbances,suggest- ing platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwtlJAK2wt patients. MPLW515UK patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

引用

页码：844 / 847

页数：4

共 35 条

[1] Thrombopoietin and platelet function [J].

Akkerman, JWN .

SEMINARS IN THROMBOSIS AND HEMOSTASIS, 2006, 32 (03) :295-304

[2] Clinical implications of the JAK2 V617F mutation in essential thrombocythemia [J].

Antonioli, E ;

Guglielmelli, P ;

Pancrazzi, A ;

Bogani, C ;

Verrucci, M ;

Ponziani, V ;

Longo, G ;

Bosi, A ;

Vannucchi, AM .

LEUKEMIA, 2005, 19 (10) :1847-1849

[3] Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia [J].

Antonioli, Elisabetta ;

Guglielmelli, Paola ;

Poli, Giada ;

Bogani, Costanza ;

Pancrazzi, Alessandro ;

Longo, Giovanni ;

Ponziani, Vanessa ;

Tozzi, Lorenzo ;

Pieri, Lisa ;

Santini, Valeria ;

Bosi, Alberto ;

Vannucchi, Alessandro M. .

HAEMATOLOGICA, 2007, 93 (01) :41-48

[4] Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment [J].

Barosi, G. ;

Mesa, R. A. ;

Thiele, J. ;

Cervantes, F. ;

Campbell, P. J. ;

Verstovsek, S. ;

Dupriez, B. ;

Levine, R. L. ;

Passamonti, F. ;

Gotlib, J. ;

Reilly, J. T. ;

Vannucchi, A. M. ;

Hanson, C. A. ;

Solberg, L. A. ;

Orazi, A. ;

Tefferi, A. .

LEUKEMIA, 2008, 22 (02) :437-438

[5] JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis [J].

Barosi, Giovanni ;

Bergamaschi, Gaetano ;

Marchetti, Monia ;

Vannucchi, Alessandro M. ;

Guglielmelli, Paola ;

Antonioli, Elisabetta ;

Massa, Margherita ;

Rosti, Vittorio ;

Campanelli, Rita ;

Villani, Laura ;

Viarengo, Gianluca ;

Gattoni, Elisabetta ;

Gerli, Giancarla ;

Specchia, Giorgina ;

Tinelli, Carmine ;

Rambaldi, Alessandro ;

Barbui, Tiziano .

BLOOD, 2007, 110 (12) :4030-4036

[6] Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].

Baxter, EJ ;

Scott, LM ;

Campbell, PJ ;

East, C ;

Fourouclas, N ;

Swanton, S ;

Vassiliou, GS ;

Bench, AJ ;

Boyd, EM ;

Curtin, N ;

Scott, MA ;

Erber, WN ;

Green, AR .

LANCET, 2005, 365 (9464) :1054-1061

[7] MPL mutations in myeloproliferative disorders:: analysis of the PT-1 cohort [J].

Beer, Philip A. ;

Campbell, Peter J. ;

Scott, Linda M. ;

Bench, Anthony J. ;

Erber, Wendy N. ;

Bareford, David ;

Wilkins, Bridget S. ;

Reilly, John T. ;

Hasselbalch, Hans C. ;

Bowman, Richard ;

Wheatley, Keith ;

Buck, Georgina ;

Harrison, Claire N. ;

Green, Anthony R. .

BLOOD, 2008, 112 (01) :141-149

[8] V617F mutation in JAK2 is associated idiopathic myelofibrosis [J].

Campbell, PJ ;

Griesshammer, M ;

Döhner, K ;

Döhner, H ;

Kusec, R ;

Hasselbalch, HC ;

Larsen, TS ;

Pallisgaard, N ;

Giraudier, S ;

Le Bousse-Kerdilès, MC ;

Desterke, C ;

Guerton, B ;

Dupriez, B ;

Bordessoule, D ;

Fenaux, P ;

Kiladjian, JJ ;

Viallard, JF ;

Brière, J ;

Harrison, CN ;

Green, AR ;

Reilly, JT .

BLOOD, 2006, 107 (05) :2098-2100

[9] Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status:: a prospective study [J].

Campbell, PJ ;

Scott, LM ;

Buck, G ;

Wheatley, K ;

East, CL ;

Marsden, JT ;

Duffy, A ;

Boyd, EM ;

Bench, AJ ;

Scott, MA ;

Vassiliou, GS ;

Milligan, DW ;

Smith, SR ;

Erber, WN ;

Bareford, D ;

Wilkins, BS ;

Reilly, JT ;

Harrison, CN ;

Green, AR .

LANCET, 2005, 366 (9501) :1945-1953

[10] Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis [J].

Chaligne, Ronan ;

James, Chloe ;

Tonetti, Carole ;

Besancenot, Rodolphe ;

Pierre Le Couedic, Jean ;

Fava, Fanny ;

Mazurier, Frederic ;

Godin, Isabelle ;

Maloum, Karim ;

Larbret, Frederic ;

Lecluse, Yann ;

Vainchenker, William ;

Giraudier, Stephane .

BLOOD, 2007, 110 (10) :3735-3743

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Characteristics and clinical correlates of MPL 515W&gt;L/K mutation in essential thrombocythemia

Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia