L3a

Primary myelofibrosis

Stem cell defect inducing increased  hematopoietic (especially abnormal megakaryocytic) Proliferation PATHOGENESIS: Abnormal megakaryocytes produce growth factors (PDGF and TGF-β) that stimulate  fibroblasts (and osteoblasts); causes marrow fibrosis,  resulting in extramedullary hematopoiesis

JAK2 50%

• Usual leukemic symptoms and signs • Particularly prominent hepatosplenomegaly due to extensive extramedullary hematopoiesis • Progresses to acute leukemia (almost always AML) in 5-10% of cases

Note: ET also involves an increase in megakaryocytes:

Essential thombocytopenia

Stem cell defect inducing predominantly  megakaryocyte/platelet overproduction

JAK2 40-50%

• Thrombocytosis (often >1,000,000); platelet dysfunction •Thromboembolism and/or bleeding complications • Progression to acute leukemia may occur, but is Uncommon

Describe what you see in the picture

Note the extensive fibrosis in this bone marrow core biopsy -- we would expect to see tear drop RBCs in the periphery 

note: the clump of megakaryocytes 

  What is the pathogenesis of this disease?

·         ↑ megakaryocytes à increase GF that stimulate fibroblasts à marrow fibrosis à extramedullary hematopoesis