Klinische Forschungsgruppe KFO 344 / Clinical Research Unit CRU 344

Mechanisms of Myelofibrosis in Myeloproliferative Neoplasms (MPN)

Myeloproliferative neoplasms (MPN) comprise Bcr-Abl negative (Polycythemia vera [PV], Essential Thrombocythemia [ET], and Primary Myelofibrosis [PMF]) and Bcr-Abl positive (Chronic Myeloid Leukemia [CML]) as well as less frequent subtypes (Chronic Neutrophilic Leukemia [CNL], Chronic Eosinophilic Leukemia [CEL], and unclassified MPN [MPN-U]). These chronic malignancies are characterized by hyperplasia of blood cells, splenomegaly, and constitutional symptoms as well as increased bone marrow fibrosis (primary or secondary myelofibrosis) and/or leukemic transformation, but the causes are largely unknown. Recent work by our consortium has shown that Gli1+ mesenchymal stromal cells (MSC) are precursors of fibrosis-causing myofibroblasts in the bone marrow. This Clinical Research Unit (CRU) has been estabilshed in order to

  • investigate mechanisms of myofibroblast development from MSC in myelofibrosis,
  • analyze changes in the bone marrow niche in MPN that are responsible for bone marrow transformation into an oncogenic entity with loss of normal hematopoiesis, and
  • identify new cellular and molecular therapeutic targets in myelofibrosis by better understanding the underlying mechanisms.
Proposed mechanisms in the stepwise reprogramming of the bone marrow niche towards an oncogenic, fibrotic unit. The involvement of the individual projects (P1-P6) of the CRU344 in the dissection of the different steps is highlighted by the number of each project. Image modified from Kramann and Schneider, Blood 2018; 131(19): 2111-2119.

More information about the project KFO 344: Mechanisms of Myelofibrosis in Myeloproliferative Neoplasms (MPN)​​​​​​​.