11.18: Hemo IV Flashcards
Another name for the chronic myeloid disorders?
- Myeloproliferative disorders
4 major myeloproliferative disorders?
“MPDs”
- CML: “Chronic myelogenous leukemia”: WBCs
- Polycythemia vera: RBCs
- Primary myelofibrosis
- “ET” Essential thrombocytosis: platelets
Commonalities in myeloproliferative disorders?
- Target cell is multipotent myeloid progenitor cell
- Differ from AML in that cells can continue to differentiate beyond blast stage
- Increased marrow cellularity and hematopoiesis w/ increased peripheral blood cell counts
- Splenomegaly
- Terminate in spent phase with marrow fibrosis and peripheral cytopenias
What is unique about CML?
- Pluripotent stem cell that can give rise to both lymphoid and myeloid cells is target
What can MPDs progress to?
Leukemia
Common pathogenic feature in all MPDs?
- Mutated constitutively active tyrosine kinase leading to growth factor independent proliferation
What is the mutation in CML?
- BCR/ABL fusion gene
What is mutation in polycythemia vera?
JAK2 point mutations
What is the mutation in ET and primary myelofibrosis?
JAK2, CALR and MPL point mutations
What does mutation in BCR/ABL fusion gene cause?
CML
What does JAK2 point mutations cause?
Polycythemia vera
What does JAK2, CALR and MPL point mutations cause?
ET
Primary myelofibrosis
Distinguishing factor in CML?
- Observation of Philadelphia chromosome via karyotyping in 90% of patients
- Mutation can be seen in myeloid stem cells as well as B and T cells
- Hints that abnormality occurs in pluripotent stem cells
What is the Philadelphia chromosome?
- Reciprocal translocation between ABL gene on chromosome 9 and BCR gene on chromosome 22
- Encodes for synthesis of protein with tyrosine kinase activity
How can you treat CML?
Tyrosine kinase inhibitors
- Gleevec/imatinib
What is see in CML marrow?
- Marked increase in neoplastic granulocytic precursors in marrow
- Bone marrow is 100% cellular w/ increased megakaryocytes
What is seen in CML periphery?
- Leukocytosis with shift to immaturity
- Thrombocytosis
- Basophilia
- Small number of circulating blasts
What is marrow cellularity of 100% characteristic of?
CML
What is the following indicative of:
- Leukocytosis with shift to immaturity
- Basophilia
- Thrombocytosis
- Small number of circulating blasts
CML
How to distinguish CML from leukemoid rxn?
CML has the following:
- WBC > 50k in all stages of maturation
- Reduced LAP score
- M:E ratio > 10 in marrow
- Splenomegaly
- 9:22 BCR/ABL
What can original presentation of CML be?
Abdominal discomfort from splenomegaly
What is accelerated phase of CML?
- Unresponsive to treatment
- Increased symptoms
- Becomes blast phase which looks like AML
What is relative polycythemia?
Occurs from dehydration or decreased plasma volume
What is absolute polycythemia?
From increase in total red cell mass
