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Chronische myeloische Neoplasien

Diagnostische Kriterien und Ausblick auf aktuelle Theapiekonzepte

Chronic myeloid neoplasms

Diagnostic criteria and current therapeutic concepts

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Zusammenfassung

Myeloproliferative Neoplasien (MPN) und weitere chronische Erkrankungen dieses Formenkreises stellen eine Subgruppe myeloischer Neoplasien dar, deren Definition nach klinischen, morphologischen und molekularen Merkmalen in der aktuellen Klassifikation der Weltgesundheitsorganisation (WHO) festgelegt wurde. Screening-Programme zum Nachweis eines BCR-ABL-Fusionsgens, von JAK2-, Thrombopoietinrezeptor- und KIT-Mutationen sind in die diagnostische Aufarbeitung eingeschlossen. Myelodysplastische/MPN-Overlap-Syndrome schließen seltene Entitäten wie die refraktäre Anämie mit Ringsideroblasten ein, die durch einen hohen Anteil von JAK2V617F-mutierten Fällen charakterisiert ist. Das Paradigma der zielgerichteten Therapie der chronischen myeloischen Leukämie mit Imatinib wird jetzt auch auf Eosinophilie-assoziierte myeloische Neoplasien mit PDGFRA-, PDGFRB- oder FGFR1-Genmutationen ausgedehnt. So konnte gezeigt werden, dass pegyliertes Interferon-α die JAK2-Allel-Last signifikant reduzieren kann. JAK2-Inhibitoren werden in klinischen Studien getestet. Die Entwicklung von auf die Pathogenese ausgerichteten diagnostischen und therapeutischen Strategien für die unterschiedlichen myeolischen Neoplasien wird in Zukunft weitere Fortschritte erzielen.

Abstract

Myeloproliferative neoplasms (MPNs) and related chronic disorders constitute a subgroup of myeloid malignancies which are defined according to clinical, morphological and molecular features by the actual World Health Organization classification of tumors of the haematopietic system. Screening procedures for a BCR-ABL fusion gene, JAK2, thrombopoietin receptor and KIT mutations are formally included in the diagnostic approach. Myelodysplastic/MPN overlap syndromes include rare entities such as refractory anemia with ringed sideroblasts characterized by a high proportion of JAK2V617F mutated cases. The paradigm of targeted treatment of chronic myeloid leukemia with imatinib has now been extended to eosinophilia-associated myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 gene mutations. Pegylated interferon-alpha has convincingly been proved to reduce the JAK2 allele burden. JAK2 inhibitor drugs are currently being tested in clinical trials. The development of pathogenesis-targeted diagnostic and therapeutic approaches to the various MPNs will continue in the future.

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Abbreviations

ALL:

Akute lymphoblastische Leukämie

AML:

Akute myeloische Leukämie

BP:

Blastenphase

CEL:

Chronische Eosinophilenleukämie

CLL:

Chronische lymphatische Leukämie

CMGM:

Chronische megakaryozytäre-granulozytäre Myelose

CML:

Chronische myeloische Leukämie

CMML:

Chronische myelomonozytäre Leukämie

CNL:

Chronische Neutrophilenleukämie

ET:

Essenzielle Thrombozythämie

HES:

Hypereosinophilensyndrom

MDS:

Myelodysplastisches Syndrom

MF:

Myelofibrose

MN:

Myeloische Neoplasie

MPN:

Myeloproliferative Neoplasie

NOS:

„Not otherwise specified“

PMF:

Primäre Myelofibrose

PV:

Polycythaemia vera

RARS-T:

Refraktäre Anämie mit Ringsideroblastose und Thrombozytose

RCMD:

Refraktäre Zytopenie mit multilineärer Dysplasie

SM-AHNMD:

Systemische Mastozytose in Assoziation mit einer klonalen hämatologischen Nicht-Mastzellerkrankung

U:

Unklassifizierbar

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  1. Institut für Pathologie, Universitätsklinikum Freiburg, Breisacherstr. 115a, 79106, Freiburg, Deutschland

    A.H. Schmitt-Graeff

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Schmitt-Graeff, A. Chronische myeloische Neoplasien. Pathologe 31, 29–41 (2010). https://doi.org/10.1007/s00292-009-1261-x

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