Flashcards in Hemtopathology IV Deck (31)
What are the 4 main types of chronic myeloproliferative disorders (MPD)?
• Chronic myelogenous leukemia (CML)
• Polycythemia vera (predominantly red blood cells)
• Essential thrombocytosis (platelets)
What is the common target of the chronic myeloproliferative disorders?
Multipotent Myeloid Progenitor Cells - CML is different though as it affects a pluripotent stem cells that gives rise to BOTH lymphoid and myeloid cells
What are some common features of the MPD?
- All can progress to acute leukemia
- "Spent phase" where marrow fibrosis and cytopenia occurs as cells are worn out
- Mutated activated tyrosine kinases
What is the tyrosine kinase mutation in CML?
What is the tyrosine kinase mutation in polycythemia vera?
ET and Primary Myelofibrosis
JAK2, CALR, MPL
What is the classic chromosome abnormality found in CML?
What is the transaction of the Philadelphia Chromosome?
This abnormality represents a reciprocal translocation between the ABL gene on chromosome 9 and the BCR gene on chromosome 22 - the BCR-ABL codes for a fusion protein with tyrosine kinase activity
What are the findings with CML?
- There is a marked increase in neoplastic granulocytic precursors in the marrow
- Bone marrow is close to 100% cellular
- Increased numbers of megakaryocytes
- Erythroid progenitors are usually normal or decreased
What is the normal proportion of RBCs to WBCs?
What is the ratio of RBCs to WBCs in CML?
It can be as low as 10:1
How can you distinguish between CML and a leukemoid reaction?
WBCs Usually >50,000
All stages of maturation
9;22 BCR-ABL mutation
WBCs Usually less than 50,000/L
Almost all mature
NO 9;22 BCR-ABL mutation
What is the LAP score in CML versus leukemoid reaction?
LAP will be reduced in CML and elevated in a leukemoid reaction
What is the onset of CML like?
What is the accelerated phase of CML?
About 50% of patients eventually enter "accelerated" phase with decreased response to treatment, increasing anemia and thrombocytopenia, sometimes striking peripheral blood basophilia, additional cytogenetic abnormalities
What is the blast phase of CML?
The accelerated phase transforms to "blast" phase or blast crisis in which picture looks like AML in about 70% (or, in about 30%, pre-B ALL or rarely pre-T ALL)
What is the drug used to treat CML?
Imatinib - ABL specific as a tyrosine kinase inhibitor and it serves to normalize the count without chemotherapy
Erythroid precursors dominate, leading to an absolute increase in red cell mass that is responsible for most of the clinical symptoms. P. vera progenitor cells have markedly decreased requirements for Erythropoietin.
What is the typical patent for polycythemia vera?
What are some of the complications of polycythemia vera?
Total blood volume accompanies the elevation in hematocrit, promoting abnormal blood flow, vascular distension and stasis. Thrombotic episodes that may lead to myocardial infarction, stroke, deep vein thrombosis, Budd-Chiari syndrome, etc.
What is the most common treatment of polycythemia vera?
What is Primary Myelofibrosis also known as?
Chronic Idiopathic Myelofibrosis
What is unique to Primary Myelofibrosis?
Unlike other CMPD, early progression to obliterating marrow fibrosis (morphologically similar to spent phase of other CMPD) form excessive collagen deposition in the bone marrow.
What is the typical patient of Primary Myelofibrosis?
Patients are usually elderly and seek medical attention mainly due to progressive anemia, splenic enlargement or other non-specific symptoms
What does the smear of primary myelofibrosis show?
Dacrocytes - tear drop cells
What is the appearance of the bone marrow in PM?
What stain is done for fibrosis in bone marrow?
Reticulin stain to visualize the collagen III that is normally not present except in PM
What is the main effect of Essential Thrombocytosis?
Proliferation predominantly of megakaryocytic lineage cells (high platelet counts)
What does blood smear of ET show?
Abnormally large platelets
What are some clinical findings of ET?
Thrombosis and hemorrhage due to the abnormalities of the platelets