Myeloproliferative Disorders & Myelodysplastic Syndrome Flashcards
What defines a myeloproliferative disorder? What do these disorders have an increased risk for? What are the four main disorders?
- these are characterized by the accumulation of mature myeloid cells
- most MPNs (myeloproliferative neoplasms) have an increased risk for hyperuricemia and gout, progressing into marrow fibrosis (“burnt out”), and transforming into an acute leukemia (“blast crisis”)
- CML (predominant proliferation of granulocytes)
- polycythemia vera (predominant proliferation of RBCs)
- essential thrombocytosis (proliferation of megakaryocytes; does not have the complications listed above)
- myelofibrosis
What genetic abnormalities commonly drive the myeloproliferative disorders? What treatment do they all share?
- vast majority of cases are driven by a JAK2 mutation (JAK2 is involved in hematopoietic growth factor signaling); except for CML (Philadelphia chromosome)
- 2nd MC mutation is in CALR gene (disruption increases the JAK-STAT pathway), 3rd is MPL (the TPO receptor)
- only a small percentage aren’t a result of one of these mutations
- all (except CML) are largely treated with cytoreductive therapy with hydroxyurea
What is polycythemia vera? How do patients classically present and what drives these symptoms? How do we treat it? What percent of cases progress into an acute leukemia?
- polycythemia vera is a myeloproliferative disorder involving the excessive proliferation of mainly RBCs (WBCs and platelets are also increased, but to a lesser degree)
- patients present with blurry vision, headache, stroke, venous thrombosis (especially Budd-Chiari syndrome), and an intense itching after a hot shower
- all symptoms are due to the resulting increased viscosity of the blood
- treated with phlebotomy and hydroxyurea
- 5% progress to acute leukemia
What are the major differentials of polycythemia vera? How can we differentiate between them?
- DDx: secondary (reactive polycythemia or ectopic secretion), relative polycythemia
- reactive (AKA appropriate absolute polycythemia): a response to hypoxia (caused by lung disease, CHF, altitude, etc.); normal plasma volume, elevated RBC mass, decreased O2 saturation, increased EPO
- ectopic (AKA inappropriate absolute): due to ectopic secretion of EPO (via RCC, Wilms tumor, HCC); normal plasma volume, elevated RBC mass, normal O2, increased EPO
- relative: due to decreased plasma volume (via dehydration, diuretics, etc.); decreased plasma volume, everything else normal
- polycythemia vera: increased plasma volume, increased RBC mass, normal O2, decreased EPO
What is essential thrombocytosis? How do patients classically present? How do we treat it? What percent of cases progress into an acute leukemia?
- essential thrombocytosis is a myeloproliferative disorder involving the excessive proliferation of abnormal platelets due to enlarged megakaryocytes
- patients have both bleeding and thrombosis formation
- (note that ET doesn’t have as great of an association with hyperuricemia/gout because platelets are anucleate)
- treated with hydroxyurea
- 1-2% progress to acute leukemia
What is myelofibrosis? What do we see on BM aspiration and blood smear? What is this the most common cause of? How do we treat it?
- myelofibrosis is a myeloproliferative disorder involving the excessive formation of scar tissue, obliterating the bone marrow’s functionality
- BM: megakaryocyte proliferation and atypia with fibrosis; is often a dry tap
- blood smear: leukoerythroblastic smear with teardrop RBCs
- this is the MCC of massive splenomegaly in patients older than 50 (because of extramedullary hematopoiesis)
- treated with ruxolitinib (a JAK2 inhibitor) and hydroxyurea
What is myelodysplastic syndrome?
- MDS is a group of clonal disorders that each result in some form of cytopenia
- initially, increased apoptosis causes a cytopenia; eventually, MDS converts into leukemia with further gene mutation (it is largely a precursor to AML)
