{"orpha":824,"name":"Primary myelofibrosis","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Agnogenic myeloid metaplasia","Idiopathic myelofibrosis","Myelofibrosis with myeloid metaplasia","Osteomyelofibrosis"],"definition":"A rare myeloproliferative neoplasm characterized by stem-cell derived clonal over proliferation of mature myeloid lineages, such as erythrocytes, leukocytes, and megakaryocytes, with variable degrees of megakaryocyte atypia, associated with reticulin and/or collagen bone marrow fibrosis, osteosclerosis, ineffective erythropoiesis, angiogenesis, extramedullary hematopoiesis, and abnormal cytokine expression.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-824/","orphanet_url":"https://www.orpha.net/en/disease/detail/824","names":{"fr":{"name":"Myélofibrose primaire","synonyms":["Myélofibrose idiopathique","Myélofibrose primitive","Myélosclérose avec métaplasie myéloïde","Osteomyélofibrose"],"definition":"Néoplasie myéloproliférative rare caractérisée par une prolifération clonale excessive dérivée de cellules souches de lignées myéloïdes matures, telles que les érythrocytes, les leucocytes et les mégacaryocytes, avec une atypie mégacaryocytaire de degré variable, associée à une fibrose réticulinique et/ou collagénique de la moelle osseuse, une ostéosclérose, une érythropoïèse inefficace, une angiogenèse, une hématopoïèse extramédullaire et une expression anormale des cytokines."},"de":{"name":"Primäre Myelofibrose","synonyms":["Agnogenische myeloide Metaplasie","Myelofibrose mit myeloischer Metaplasie","Myelofibrose, idiopathische","Osteomyelofibrose","PMF"],"definition":"Ein seltene myeloproliferative Neoplasmie, die durch eine von Stammzellen abgeleitete klonale Überproliferation reifer myeloischer Linien wie Erythrozyten, Leukozyten und Megakaryozyten mit unterschiedlichem Grad an Megakaryozyten-Atypie gekennzeichnet ist und mit Retikulin- und/oder Kollagen-Knochenmarkfibrose, Osteosklerose, ineffektiver Erythropoese, Angiogenese, extramedullärer Hämatopoese und abnormaler Zytokinexpression einhergeht."},"es":{"name":"Mielofibrosis primaria","synonyms":["Metaplasia mieloide agnogénica","Mielofibrosis con metaplasia mieloide","Mielofibrosis idiopática","Osteomielofibrosis"],"definition":"Es una neoplasia mieloproliferativa poco frecuente caracterizada por el exceso de proliferación clonal de líneas mieloides maduras derivadas de células madre, como eritrocitos, leucocitos y megacariocitos, con grados variables de atipia megacariocítica asociados a fibrosis reticulínica o colágena de la médula ósea, osteosclerosis, eritropoyesis ineficaz, angiogénesis, hematopoyesis extramedular y expresión anómala de citoquinas."},"it":{"name":"Mielofibrosi primitiva","synonyms":["Mielosclerosi con metaplasia mieloide","Metaplasia mieloide agnogenica","Mielofibrosi con metaplasia mieloide","Mielofibrosi idiopatica"],"definition":"La mielofibrosi primitiva (PMF) è una neoplasia mieloproliferativa rara, caratterizzata da iperproliferazione clonale di linee mieloidi mature derivate dalle cellule staminali (eritrociti, leucociti e magacariociti) con variabili atipie dei megacariociti, associate a fibrosi del midollo osseo da reticolina e/o collagene, osteosclerosi, eritropoiesi inefficace, angiogenesi, ematopoiesi extramidollare ed anomala espressione delle citochine."},"nl":{"name":"Primaire myelofibrose","synonyms":["Agnogene myeloïde metaplasie","Idiopathische myelofibrose","Myelofibrose met myeloïde metaplasie","Myelosclerose met myeloïde metaplasie","Osteomyelofibrose"],"definition":"Een zeldzaam myeloproliferatief neoplasma gekarakteriseerd door excessieve klonale proliferatie van rijpe myeloïde cellijnen afgeleid van stamcellen, zoals erytrocyten, leukocyten, en megakaryocyten, met variabele gradaties van megakaryocytaire atypie, geassocieerd met reticuline en/of collageen fibrose in beenmerg, osteosclerose, ineffectieve erytropoëse, angiogenese, extramedullaire hematopoëse, en abnormale expressie van cytokinen."},"pt":{"name":"Mielofibrose com metaplasia mielóide","synonyms":["Mielofibrose idiopática"],"definition":"Uma neoplasia mieloproliferativa rara caracterizada por superproliferação clonal derivada de células estaminais de linhagens mieloides maduras, como eritrócitos, leucócitos e megacariócitos, com graus variáveis &#8203;&#8203;de atipia de megacariócitos, associada a fibrose da medula óssea de reticulina e/ou colagénio, osteosclerose, eritropoiese ineficaz, angiogénese, hematopoiese extramedular e expressão anormal de citocinas."},"pl":{"name":"Mielofibroza z metaplazją szpiku","synonyms":["Agnogenic myeloid metaplasia","Mielofibroza idiopatyczna","Mielofibroza pierwotna","Mieloskleroza z metaplazją szpiku"]},"cs":{"name":"Myelofibróza s myeloidní metaplázií","synonyms":["Agnogenní myeloidní metaplázie","Idiopatická myelofibróza","Myeloskleróza s myeloidní metaplázií","Primární myelofibróza"]},"uk":{"name":"Первинний мієлофіброз","synonyms":["Агногенна мієлоїдна метаплазія","Ідіопатичний мієлофіброз","Мієлофіброз з мієлоїдною метаплазією","Остеомієлофіброз"],"definition":"A rare myeloproliferative neoplasm characterized by stem-cell derived clonal over proliferation of mature myeloid lineages, such as erythrocytes, leukocytes, and megakaryocytes, with variable degrees of megakaryocyte atypia, associated with reticulin and/or collagen bone marrow fibrosis, osteosclerosis, ineffective erythropoiesis, angiogenesis, extramedullary hematopoiesis, and abnormal cytokine expression."},"zh":{"name":"原发性骨髓纤维化","synonyms":["骨髓纤维化伴髓样化生"]},"tr":{"name":"Primer miyelofibroz","synonyms":["Osteomiyelofibroz","İdiyopatik miyelofibroz","Agnojenik miyeloid metaplazi","Miyeloid metaplazili miyelofibroz"]}},"xrefs":[{"source":"OMIM","code":"254450","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D47.4","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"2A20.2","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"336704235"},{"source":"MONDO","code":"0009692","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D055728","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0001815","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"8618","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10077161","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":250908,"name":"Rare neoplastic disease"},"parents":[{"orpha":98274,"name":"Myeloproliferative neoplasm","classifications":[194,202,233]},{"orpha":164823,"name":"Rare acquired aplastic anemia","classifications":[194,233]}],"children":[],"genes":[{"symbol":"CALR","name":"calreticulin","gene_type":"gene with protein product","association":"Disease-causing somatic mutation(s) in","status":"Assessed","source":"24325256[PMID]_24325359[PMID]","hgnc":"1455","ensembl":"ENSG00000179218","omim":"109091","loci":["19p13.13"]},{"symbol":"JAK2","name":"Janus kinase 2","gene_type":"gene with protein product","association":"Disease-causing somatic mutation(s) in","status":"Assessed","source":null,"hgnc":"6192","ensembl":"ENSG00000096968","omim":"147796","loci":["9p24.1"]},{"symbol":"MPL","name":"MPL proto-oncogene, thrombopoietin receptor","gene_type":"gene with protein product","association":"Disease-causing somatic mutation(s) in","status":"Assessed","source":"16834459[PMID]_16868251[PMID]","hgnc":"7217","ensembl":"ENSG00000117400","omim":"159530","loci":["1p34.2"]},{"symbol":"TET2","name":"tet methylcytosine dioxygenase 2","gene_type":"gene with protein product","association":"Disease-causing somatic mutation(s) in","status":"Assessed","source":"19557078[PMID]_19262601[PMID]","hgnc":"25941","ensembl":"ENSG00000168769","omim":"612839","loci":["4q24"]}],"genes_via_subtypes":[],"inheritance":["Not applicable"],"onset":["Adult"],"prevalence":[{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Europe","status":"Validated","source":"[EXPERT]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":3.0,"area":"Europe","status":"Validated","source":"European Medicines Agency[OTHER]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-05-02","source":"30683837[PMID]_30805227[PMID]_27830539[PMID]_27870387[PMID]_9766805[PMID]_7436463[PMID]","terms":[{"hpo":"HP:0005561","label":"Abnormality of bone marrow cell morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012143","label":"Abnormal megakaryocyte morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001871","label":"Abnormality of blood and blood-forming tissues","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025142","label":"Constitutional symptom","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012378","label":"Fatigue","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000980","label":"Pallor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001892","label":"Abnormal bleeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001977","label":"Abnormal thrombosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002039","label":"Anorexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004420","label":"Arterial thrombosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031020","label":"Bone marrow hypercellularity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003388","label":"Easy fatigability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031364","label":"Ecchymosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001978","label":"Extramedullary hematopoiesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001945","label":"Fever","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030157","label":"Flank pain","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001974","label":"Increased total leukocyte count","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011134","label":"Low-grade fever","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002716","label":"Lymphadenopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001876","label":"Pancytopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000967","label":"Petechiae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004447","label":"Poikilocytosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001409","label":"Portal hypertension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000979","label":"Purpura","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001894","label":"Thrombocytosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004936","label":"Venous thrombosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004326","label":"Cachexia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001028","label":"Hemangioma","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004377","label":"Hematological neoplasm","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0025435","label":"Increased circulating lactate dehydrogenase concentration","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0030057","label":"Autoimmune antibody positivity","frequency":"Excluded (0%)","criteria":null}]}}