{"id":842,"date":"2015-06-04T00:50:37","date_gmt":"2015-06-03T22:50:37","guid":{"rendered":"http:\/\/www.pjh.fr\/wordpress\/?p=842"},"modified":"2015-06-04T00:50:37","modified_gmt":"2015-06-03T22:50:37","slug":"polyglobulie-primitive-maladie-de-vaquez-et-thrombocytemie-essentielle-mise-a-jour-2015","status":"publish","type":"post","link":"http:\/\/www.pjh.fr\/wordpress\/?p=842","title":{"rendered":"Polyglobulie primitive (maladie de Vaquez) et thrombocyt\u00e9mie essentielle : mise \u00e0 jour 2015"},"content":{"rendered":"<h1>Polyglobulie primitive et Thrombocyt\u00e9mie essentielle :\u00a0diagnostic, stratification du risque et prise en charge, mise \u00e0 jour 2015<\/h1>\n<p><em><strong>R\u00e9f\u00e9rence bibliographique :\u00a0American Journal of Hematology, Vol. 90, No. 2, February 2015 =&gt; <a href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.23895\/full\" target=\"_blank\">Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management<\/a><\/strong><\/em><\/p>\n<h2>Introduction<\/h2>\n<p>Les syndromes my\u00e9loprolif\u00e9r\u00e9atifs (SMP) d\u00e9sign\u00e9es \u00e9galement par le terme de n\u00e9oplasies my\u00e9loprolif\u00e9ratives \u00a0(traduction de <strong>Myeloproliferative neoplasms<\/strong> (MPN) de la WHO Classification) sont une des 4 entit\u00e9s des h\u00e9mopathies malignes my\u00e9lo\u00efdes (les autres \u00e9tant les leuc\u00e9mies aigu\u00ebs my\u00e9lo\u00efdes, les syndromes my\u00e9lodysplasiques (MDS) et les formes fronti\u00e8res MDS\/MPN).<\/p>\n<p>On distingue aujourd&rsquo;hui 3\u00a0groupes de MPN :<\/p>\n<ol>\n<li><strong>MPN bcr-abl1 n\u00e9gatifs :<\/strong>\n<ol>\n<li>Polyglobulie primitive (polycythemia vera : PV) ou maladie de Vaquez<\/li>\n<li>My\u00e9lofibrose primitive (Primary myelofibrosis : PMF) ou spl\u00e9nom\u00e9galie my\u00e9lo\u00efde<\/li>\n<li>PMF pr\u00e9-fibrotique<\/li>\n<li>Thrombocyt\u00e9mie essentielle (TE)<\/li>\n<\/ol>\n<\/li>\n<li><strong>Leuc\u00e9mie my\u00e9lo\u00efde chronique (LMC), BCR-ABL1 positive<\/strong><\/li>\n<li><strong>Autres MPN :<\/strong>\n<ol>\n<li>Leuc\u00e9mie chronique \u00e0 neutrophiles<\/li>\n<li>Leuc\u00e9mie chronique \u00e0 \u00e9osinophiles, sans autre sp\u00e9cification<\/li>\n<li>Mastocytose<\/li>\n<li>MPN inclassables<\/li>\n<\/ol>\n<\/li>\n<\/ol>\n<h2>G\u00e9n\u00e9tique des SMP BCR-ABL n\u00e9gatifs<\/h2>\n<p>prolif\u00e9rations clonales d\u00e9rivant de cellules souches avec pr\u00e9sence de mutations <strong>mutuellement exclusives<\/strong> de <strong>JAK2, calreticuline (CALR) ou MPL<\/strong>.<\/p>\n<p>&nbsp;<\/p>\n<table class=\"aligncenter\" style=\"height: 163px;\" border=\"1\" width=\"415\" cellspacing=\"1\" cellpadding=\"5\">\n<tbody>\n<tr style=\"background-color: #d1d1d1;\">\n<td><\/td>\n<td>Jak2V617F<\/td>\n<td>Jak2 exon 12<\/td>\n<td>CALR<\/td>\n<td>MPL (1p34)<br \/>\nexon 10<\/td>\n<\/tr>\n<tr>\n<td>PV<\/td>\n<td>96%<\/td>\n<td>3%<\/td>\n<td>rare<\/td>\n<td>rare<\/td>\n<\/tr>\n<tr>\n<td>ET<\/td>\n<td>55%<\/td>\n<td>rare<\/td>\n<td>15-24%<\/td>\n<td>4%<\/td>\n<\/tr>\n<tr>\n<td>PMF<\/td>\n<td>65%<\/td>\n<td>rare<\/td>\n<td>25-35%<\/td>\n<td>8%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>mutations le plus souvent <strong>somatiques<\/strong> mais il existe des mutations germinales\u00a0responsables de formes familiales :<\/p>\n<ul style=\"list-style-type: circle;\">\n<li>MPL S505N : mutation germinale\u00a0(formes h\u00e9r\u00e9ditaires de thrombocytoses) ou somatique<\/li>\n<li>TE h\u00e9r\u00e9ditaires : mutation germinale de JAK2 (JAK2V617I) : formes associ\u00e9es \u00e0 des complications thrombo-emboliques mais pas d&rsquo;\u00e9volution en my\u00e9lofibrose ou de transformation leuc\u00e9mique<\/li>\n<\/ul>\n<p>autres mutations retrouv\u00e9es : TET2, IDH, <strong>ASXL1<\/strong>, DNMT3A<\/p>\n<p><strong>Impact\u00a0clinique de ces mutations :<\/strong><\/p>\n<ul style=\"list-style-type: disc;\">\n<li><strong>Mutation JAK2 V617F :<\/strong>\n<ul>\n<li>PV et TE : pas d&rsquo;impact sur survie et risque de transformation en LA<\/li>\n<li>TE : +\u00a0thrombose art\u00e9rielle \u2191\u00a0\/ &#8211; my\u00e9lofibrose\u00a0\u2193<\/li>\n<li>PV : proportion all\u00e8les mut\u00e9es \u00e9lev\u00e9e\u00a0: prurit +, \u00e9volution en my\u00e9lofibrose +<\/li>\n<\/ul>\n<\/li>\n<li><strong>Mutations exon 12 de Jak 2 :<\/strong>\n<ul>\n<li>hyperplasie \u00e9rythro\u00efde pr\u00e9dominante<\/li>\n<li>dosage d&rsquo;EPO sub-normal<\/li>\n<li>patient plus jeune<\/li>\n<li>m\u00eame pronostic que Jak2 V617F<\/li>\n<\/ul>\n<\/li>\n<li><strong>Mutations CALR<\/strong>\n<ul>\n<li>TE : + jeune, sexe masculin, plaquettes + \u00e9lev\u00e9es, h\u00e9moglobine et leucocytes &#8211; \u00e9lev\u00e9s, moins d&rsquo;\u00e9v\u00e9nements thrombotiques<\/li>\n<li>PMF : + jeune, plaquettes + \u00e9lev\u00e9es, profil de risque meilleur, moins d&rsquo;an\u00e9mie, d&rsquo;hyperleucocytose et de mutations du spliceosome (notamment SRSF2 et U2AF1 : prono d\u00e9favorable)<\/li>\n<\/ul>\n<\/li>\n<li><strong>Mutations MPL : ???\u00a0<\/strong>(+ \u00e2g\u00e9, femme, hb + basse, plq + hautes), pas d&rsquo;association \u00e0 survie ou transfo leuc\u00e9miques<\/li>\n<\/ul>\n<h2>Diagnostic<\/h2>\n<table style=\"height: 302px;\" width=\"721\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" colspan=\"7\"><strong>Crit\u00e8res diagnostiques OMS 2008<\/strong><\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td><\/td>\n<td>PV<\/td>\n<td><\/td>\n<td>TE<\/td>\n<td><\/td>\n<td>PMF<\/td>\n<\/tr>\n<tr>\n<td>Crit\u00e8res majeurs<\/td>\n<td>1<\/td>\n<td>hb &gt; 18,5 (homme)<br \/>\nhb &gt; 16,5 (femme)<\/p>\n<p>ou hb ou ht &gt; 99\u00e8me percentile<\/p>\n<p>ou VGI &gt; 125%<\/p>\n<p>ou +2g\/dL par rapport \u00e0 taux de base<\/td>\n<td>1<\/td>\n<td>Plq &gt; 450 G\/L<\/td>\n<td>1<\/td>\n<td>prolif\u00e9ration et atypies m\u00e9gacaryocytaires accompagn\u00e9es par une fibrose soit r\u00e9ticulinique soit collag\u00e8ne<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td>2<\/td>\n<td>Jak2 v617F ou exon 12<\/td>\n<td>2<\/td>\n<td>prolif\u00e9ration m\u00e9gacaryocytaire avec morphologie grande et mature<\/td>\n<td>2<\/td>\n<td>Pas de crit\u00e8res pour LMC, PV ou MDS<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td><\/td>\n<td><\/td>\n<td>3<\/td>\n<td>Pas de crit\u00e8res pour LMC, PV PMF, MDS<\/td>\n<td>3<\/td>\n<td>Jak2 V617F ou autre marqueur de clonalit\u00e9<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td><\/td>\n<td><\/td>\n<td>4<\/td>\n<td>Jak2 V617F ou autre marqueur de monoclonalit\u00e9 ou pas de thrombocytose r\u00e9actionnelle<\/td>\n<td><\/td>\n<td><\/td>\n<\/tr>\n<tr>\n<td>Crit\u00e8res mineurs<\/td>\n<td>1<\/td>\n<td>BOM : prolif\u00e9ration des 3 lign\u00e9es<\/td>\n<td><\/td>\n<td><\/td>\n<td>1<\/td>\n<td>Erythromy\u00e9l\u00e9mie<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td>2<\/td>\n<td>EPO sub-normale<\/td>\n<td><\/td>\n<td><\/td>\n<td>2<\/td>\n<td>LDH augment\u00e9es<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td>3<\/td>\n<td>Pousse pr\u00e9curseurs \u00e9rythro\u00efdes<\/td>\n<td><\/td>\n<td><\/td>\n<td>3<\/td>\n<td>An\u00e9mie<\/td>\n<\/tr>\n<tr>\n<td><\/td>\n<td><\/td>\n<td><\/td>\n<td><\/td>\n<td><\/td>\n<td>4<\/td>\n<td>Spl\u00e9nom\u00e9galie palpable<\/td>\n<\/tr>\n<tr>\n<td>diagnostic si<\/td>\n<td><\/td>\n<td>M1+M2<\/p>\n<p>ou<\/p>\n<p>M1 + m2<\/td>\n<td><\/td>\n<td>M1+M2+M3+M4<\/td>\n<td><\/td>\n<td>M1+M2+M3+2 mineurs<\/td>\n<\/tr>\n<tr>\n<td>explorations n\u00e9cessaires<\/td>\n<td><\/td>\n<td>NFS \u00b1 VGI<br \/>\nJak2<br \/>\nEPO<\/td>\n<td><\/td>\n<td>NFS,\u00a0BOM, JAK2<br \/>\nBCR-ABL\/Cytog\u00e9n\u00e9tique<br \/>\n\u00b1 VGI, LDH<\/td>\n<td><\/td>\n<td>NFS, BOM, JAK2, LDH<br \/>\nBCR-ABL\/Cytog\u00e9n\u00e9tique<br \/>\nRate<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>Algorithme diagnostique \u00e0 partir des mutations :<\/strong><\/p>\n<p><img loading=\"lazy\" class=\"inline-figure__image inline-figure__image--js \" src=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0001.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyflNs8AYZfKVamdp8p%2BzDSfs%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" alt=\"Figure\u00a01. \" width=\"\" height=\"\" data-original=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0001.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyflNs8AYZfKVamdp8p%2BzDSfs%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" \/><\/p>\n<p><strong>PV<br \/>\n<\/strong>mutation JAK2 =&gt; diff\u00e9rencie PV des autres causes d&rsquo;augmentation d&rsquo;h\u00e9matocrite<br \/>\nEPO basse + JAK2 V617F+ =&gt; diagnostic<br \/>\nEPO basse + JAK2 V617F- =&gt; mutations exon 12<\/p>\n<p>diagnostics diff\u00e9rentiels :<\/p>\n<p><img loading=\"lazy\" class=\"inline-figure__image inline-figure__image--js \" src=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0002.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyfopnz%2BEez8r2XPnlxkR8vNs%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" alt=\"Figure\u00a02. \" width=\"\" height=\"\" data-original=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0002.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyfopnz%2BEez8r2XPnlxkR8vNs%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" \/><\/p>\n<p><strong>PV masqu\u00e9e :<\/strong>\u00a0JAK2+ et BOM morphologie de PV mais Hb entre 16 et 18,5 g\/dL (homme) et 15 et 16,5 (femme). Seuil pour diff\u00e9rencier TE et PV masqu\u00e9e : hb 16,5 g\/dL (homme) &#8211; 16 g\/dL (femme) ou h\u00e9matocrite 49% (homme) &#8211; 48% (femme).<br \/>\nint\u00e9gration n\u00e9cessaire de la BOM dans les futurs crit\u00e8res\u00a0majeurs<\/p>\n<p><strong>PMF pr\u00e9fibrotique<\/strong> : int\u00e9r\u00eat de la BOM (notamment pour la diff\u00e9rencier d&rsquo;une TE)<\/p>\n<h2>Facteurs de risque (survie\/my\u00e9lofibrose\/transformation leuc\u00e9mique)<\/h2>\n<p>Survie m\u00e9diane : TE 20 ans, PV 14 ans, PMF : 6 ans<br \/>\nsi patient &lt; 60 ans : 33, 24 et 15 ans<\/p>\n<p><strong>TE :\u00a0<\/strong>Pas d&rsquo;impact de JAK2 et CALR<br \/>\n\u00e2ge, leucocytose, thromboses<\/p>\n<p><strong>Taux de transformation leuc\u00e9mique \u00e0 20 ans<\/strong> &lt; 10% our PV, 5% TE<br \/>\n<strong>Taux de transformation en my\u00e9lofibrose :<\/strong> sup\u00e9rieurs<\/p>\n<h2><strong>Traitement adapt\u00e9 au risque<\/strong><\/h2>\n<p><img loading=\"lazy\" class=\"inline-figure__image inline-figure__image--js \" src=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0003.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyfpLSEP7Xd51DikjNqhbvlw8%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" alt=\"Figure\u00a03. \" width=\"\" height=\"\" data-original=\"http:\/\/api.onlinelibrary.wiley.com\/asset\/v1\/doi\/10.1002%2Fajh.23895\/asset\/image_n%2Fajh23895-fig-0003.png?l=SkaBT8QEx2rWMM9THFln4D%2BuPuDHWl9%2BMRXZeU4xuewU6j6IlhLyfpLSEP7Xd51DikjNqhbvlw8%3D&amp;s=%225a0aaf160ff942889a425c97034c4492%22&amp;a=wol\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<br \/>\n<\/p>\n<div class=\"pdf24Plugin-cp\"> \t<form name=\"pdf24Form0\" method=\"post\" action=\"https:\/\/doc2pdf.pdf24.org\/wordpress.php\" target=\"pdf24PopWin\" onsubmit=\"var pdf24Win = window.open('about:blank', 'pdf24PopWin', 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\/> \t\t<a href=\"https:\/\/www.pdf24.org\" target=\"_blank\" title=\"www.pdf24.org\" rel=\"nofollow\"><img src=\"http:\/\/www.pjh.fr\/wordpress\/wp-content\/plugins\/pdf24-post-to-pdf\/img\/pdf_32x32.png\" alt=\"\" border=\"0\" height=\"32\" \/><\/a> \t\t<span class=\"pdf24Plugin-cp-space\">&nbsp;&nbsp;<\/span> \t\t<span class=\"pdf24Plugin-cp-text\">Envoyer l'article en PDF<\/span> \t\t<span class=\"pdf24Plugin-cp-space\">&nbsp;&nbsp;<\/span> \t\t<input class=\"pdf24Plugin-cp-input\" style=\"margin: 0px;\" type=\"text\" name=\"sendEmailTo\" placeholder=\"Entrez l'adresse e-mail\" \/> \t\t<input class=\"pdf24Plugin-cp-submit\" style=\"margin: 0px;\" type=\"submit\" value=\"Envoyer\" \/> \t<\/form> <\/div>","protected":false},"excerpt":{"rendered":"<p>Polyglobulie primitive et Thrombocyt\u00e9mie essentielle :\u00a0diagnostic, stratification du risque et prise en charge, mise \u00e0 jour 2015 R\u00e9f\u00e9rence bibliographique :\u00a0American Journal of Hematology, Vol. 90, No. 2, February 2015 =&gt; Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management Introduction Les syndromes my\u00e9loprolif\u00e9r\u00e9atifs (SMP) d\u00e9sign\u00e9es \u00e9galement par le terme de n\u00e9oplasies my\u00e9loprolif\u00e9ratives 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