Myeloproliferative Neoplasms Flashcards
What cell line predominates the marrow with polycythemia rubra vera?
RBCs
What cell line predominates in marrow with CML?
WBCs
What cell line predominates in marrow w/ primary myelofibrosis
Megakaryocytes
What cell line predominates in marrow w/ essential thrombocytopenia
Megakaryocytes
Particularly with CML, peripheral blood w/ MPN show?
Increased numbers of basophils or eosinophils
What MPN is not characterized by a mutation involving JAK2?
CML
Prolactin uses what pathway?
JAK-STAT signaling pathway
CML
Pathological presentation
Marrow is markedly hypercellular w/ increase in all cell lines - but no dysplastic changes present
Peripheral smear - increased WBCs - mostly neutrophils, bands and metamyelocytes may also be present
May have increased basophils/eosinophils
Differential of markedly increased neutrophils in peripheral blood is leukmoid reaction - LAP (leukocyte alkaline pohsphatase) score differentiates (CML - LAP is markedly decreased or absent, with leukemoid reaction it is increased)
CML
Genetic cause
t(9;22) - Philadelphia chromosome
oncogene c-able on chromosome 9
breakpoint cluster region on chromosome 22
Results in the BCR-ABL fusion gene and unregulated expression of the ABL1 gene - results in formation of fusion protein P210 that is a nonreceptor tyrosine kinase
Imatinib
aka Gleevec
Selective tyrosine kinase inhibitor used to Tx CML
Also used to Tx GI stromal tumors
Polycythemia rubra vera
Excessive proliferation of erythroid, granulocytic, and megakaryocytic precursors derived from a single stem cell
Erythroid series dominates but hyperplasia of all elements is present
High cell turnover increases risk of hyperurecemia and gout
Absolute increase in RBC mass - increases hematocrit and blood viscosity
Hyperviscosity syndrome
Seen in polycythemia rubra vera - congestion may cause liver/spleen to be enlarged or face to appear red
Thrombotic complications (thrombosis of the hepatic vein may produce Budd-Chiari syndrome)
Pruritus and peptic ulceration are common
Polycythemia rubra vera
Genetic cause
GOF mutation in JAK2 - increased bone marrow sensitivity to growth factors (i.e. erythropoietin/thrombopoietin)
JAK2 gene codes for non-receptor tyrosine kinase in hematopoietin progenitor cells
Increased, uncontrolled proliferation of myeloid cell lines - increased RBC mass suppresses secretion of EPO by kidneys (EPO levels decrease)
Pt’s have normal oxygen sat. - differentiates between PV and secondary polycythemia caused by chronic hypoxia
Primary myelofibrosis
aka myelofibrosis w/ myeloid metaplasia
GOF mutation in JAK2 - leads to persistent activation of STAT proteins
Marrow shows marked fibrosis w/ increased retibulin
Megakaryocytes increased in number - fibrosis is secondary to PDGF and other factors released from megakaryocytes
Immature white blood cells (e.g., myelocytes) and immature red blood cells (e.g., nucleated red blood cells) can be seen in the peripheral smear, this being called leukoerythroblastosis.
Teardrop red blood cells are also seen in the peripheral smear. Teardrop cells reflect the altered bone marrow architecture, which causes red blood cells to become deformed as they leave the marrow to enter the circulation.
Essential thrombocythemia
GOF of JAK2 - permanently activating the thrombopoietin receptor - resulting in increased platelet production and thrombocytosis
Platelets are functionally abnormally - causes predisposition to bleeding/clotting abnormalities
Pt’s may have Hx of venous thromboembolism and spontaneous abortion
Tx includes hydroxyurea (which will result in an increase in circulating fetal hemoglobin), IFN-alpha, or thromboprophylaxis w/ aspirin
