Myeloproliferative Syndrome: Polycythaemia vera, essentielle Thrombozythämie, Osteomyelofibrose

Myeloproliferative Syndrome sind hämatopoietische Stammzellerkrankungen, die zur autonomen Proliferation einer oder mehrer Blutzellreihen führen. Sie werden wegen gemeinsamer klinischer und hämatologischer Merkmale, ihrer klonalen Hämatopoiese und der genetischen Instabilität mit unterschiedlicher Transformationstendenz in eine akute Leukämie als Gruppe verwandter hämatopoietischer Neoplasien zusammengefasst. In der vorliegenden Übersicht werden relevante Aspekte der klinischen Präsentation und Prognose, sowie aktuelle diagnostische und therapeutische Maßnahmen der Polycythaemia vera, Essentiellen Thrombozythämie und Chronisch Idiopathischen Myelofibrose diskutiert.

Download Full-text

Role of the activating mutation Val617Phe of Janus kinase 2 gene in myeloproliferative diseases and significance of its detection

Orvosi Hetilap ◽

10.1556/oh.2007.27860 ◽

2007 ◽

Vol 148 (5) ◽

pp. 203-210 ◽

Cited By ~ 6

Author(s):

Hajnalka Andrikovics ◽

Anikó Szilvási ◽

Nóra Meggyesi ◽

Viktória Király ◽

Gabriella Halm ◽

...

Keyword(s):

Unknown Origin ◽

Janus Kinase ◽

Polycythaemia Vera ◽

Essential Thrombocythaemia ◽

Janus Kinase 2 ◽

Idiopathic Myelofibrosis ◽

Cell Counts ◽

Myeloproliferative Syndrome ◽

Activating Mutation

The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoetic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythaemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology. The goal of the present work was to establish simple molecular genetic techniques for the routine testing of Janus kinase 2 gene Val617Phe mutation, and to compare the clinical phenotypes of Val617Phe mutation positive and negative myeloproliferative syndromes. We employed the allele specific polymerase chain technique for detection of Val617Phe mutation in 252 patients with myeloproliferative syndrome. We measured Val617Phe frequency as 85,4% (117/137) in polycytaemia vera, 56,6% (56/99) in essential thrombocythaemia, and 87,5% (14/16) in idiopathic myelofibrosis. We found significantly elevated hemoglobin levels and white blood cell counts (measured at the time of diagnosis) in Val617Phe-positive polycythaemia vera and essential thrombocythaemia patient groups compared to Val617Phe-negative patients. However, the frequencies of splenomegaly and other complications (thrombosis, bleeding, transformation to acute leukemia) were not significantly different between the mutation-positive and negative groups. In conclusion, the non-invasive mutation analysis of the Janus kinase 2 Val617Phe is suitable for routine laboratory application and helps the differential diagnosis of myeloproliferative syndrome. Althought the exact role of Val617Phe mutation testing has not yet been identified on the basis of a broad professional consensus, the testing is suggested in cases of erythrocytoses and thrombocytoses of unknown origin.

Download Full-text

Ruxolitinib – eine additive Therapieoption?

Onkologische Welt ◽

10.1055/s-0038-1670944 ◽

2018 ◽

Vol 09 (04) ◽

pp. 169-169

Author(s):

Helga Vollmer ◽

M. A. München

Keyword(s):

Polycythaemia Vera ◽

Essentielle Thrombozythämie

Zusammenfassung Belastende Symptome wie potenziell lebensbedrohende thromboembolische Kompli-kationen und Splenomegalie sind typisch für eine Polycythaemia vera (PV) und eine Essentielle Thrombozythämie (ET). Wichtigstes Therapieziel ist die Reduktion des Risikos thromboembolischer Ereignisse, nicht zuletzt von Lungenembolie, kardiovas-kulären Komplikationen und Schlaganfall, durch Senkung des Hämatokrit-Wertes auf unter 45 %.

Download Full-text

Chronisch myeloproliferative Erkrankungen bei Kindern und Jugendlichen

Kinder- und Jugendmedizin ◽

10.1055/s-0037-1617809 ◽

2004 ◽

Vol 04 (01) ◽

pp. 25-30 ◽

Cited By ~ 1

Author(s):

Meinolf Suttorp

Keyword(s):

Polycythaemia Vera ◽

Pädiatrische Patienten ◽

Myeloproliferative Erkrankungen ◽

Myeloische Leukämie ◽

Chronisch Myeloische Leukämie ◽

Somatische Mutation ◽

Hämatopoetische Stammzelle ◽

Essenzielle Thrombozythämie ◽

Who Klassifikation

ZusammenfassungAls chronisch myeloproliferative Erkrankungen (CMPE) werden die essenzielle Thrombozythämie (ET), die Polycythaemia vera (PV), die idiopathische Myelofibrose (IM) und die chronisch myeloische Leukämie (CML) zusammengefasst. Gemeinsame Ursache ist eine primäre somatische Mutation, welche eine hämatopoetische Stammzelle mit einem klonalen Proliferationsvorteil ausstattet. Die einzelnen Entitäten sind durch die Proliferation von einer oder mehreren myeloischen Zellreihen (Granulopoese, Erythropoese oder Megakarypoese) mit relativ normaler, effektiver Ausreifung charakterisiert. Der Nachweis des Philadelphia-Chromosoms trennt die CML scharf von den anderen CMPE ab. Die extreme Seltenheit einiger Entitäten und zum Teil Schwierigkeiten bei der Klassifikation bedingen für pädiatrische Patienten schwankende Angaben zur Inzidenz von 0,05-0,40 pro 100 000. Eine moderne WHO-Klassifikation der CMPE wurde in den letzten Jahren für die internistische Hämatologie etabliert, welcher auch die pädiatrische Einteilung folgt.

Download Full-text

Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645964 ◽

1987 ◽

Vol 58 (02) ◽

pp. 753-757 ◽

Cited By ~ 33

Author(s):

M F López-Fernández ◽

C López-Berges ◽

R Martín ◽

A Pardo ◽

F J Ramos ◽

...

Keyword(s):

Von Willebrand Factor ◽

Proteinase Inhibitors ◽

Relative Proportion ◽

Variable Degree ◽

Bleeding Diathesis ◽

Myeloproliferative Syndrome ◽

Von Willebrand ◽

Willebrand Factor

SummaryThe multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Download Full-text