CML Presentation
In what age group is a CML diagnosis most commonly made in the U.S.?
Middle-age (median of 55)
What are possible causes for CML?
Ionizing radiation
Medications with the suffix -tinib inhibit what?
Tyrosine kinases (ex: BCR-ABL RTK)
Increased WBC, decreased (typically) RBC, altered platelets
What risk factors for CML does Mr. Davis present with?
None
List the cells that are overproliferated in CML (50 points each)
Granulocytes: basophils, eosinophils, neutrophils
Monocytes
Platelets
Erythrocytes
(see slide 4)
Overexpression of BCR-ABL RTK leads to what?
Cell proliferation and decreased apoptosis (characteristic of cancer cells)
What does it mean to have an RT-PCR finding outside of the standard?
More mRNA or protein that had resulted
What GI exam finding(s) are common for patients that are diagnosed with CML
Splenomegaly
What is the enzymatic difference in the abnormal protein coded for by the BCR-ABL fusion gene?
Abnormal = constitutively active
Normal: requires activation
See Slide 3!
What is the main difference between imatinib and dasatinib?
Dasatinib is less specific than imatinib, and is capable of binding to multiple conformations of RTK -> overcomes resistance to imatinib
(see slide 2)
Philadelphia Chromosome
What are common symptoms associated with untreated CML patients?
Describe the genetic mutation that causes CML and where does it occur in the cell cycle?
Mutation: reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome)
Cell cycle phase: Meiosis 1
What is the most common mechanism of resistance to imatinib?
Mutations in the kinase domain of the RTK --> leads to reactivation of BCR-ABL signaling
Why was a bone marrow biopsy ordered for Mr. Davis?
To better monitor blood cell counts in response to leukemia medications
What are possible treatment options for CML?
Medications: imatinib, dastinib
Bone marrow transplant, allogenic stem-cell transplant
Differentiate between accelerated and chronic myeloid leukemia
Chronic: Increasing WBC, increasing hepatosplenomegaly, increased basophils (less than 10% blasts)
Accelerated: one of the above factors unresponsive to treatment (refers to blasts being between 15-30% of the cells)
What hematological effects are common with dasatinib? Why?
Anemia, neutropenia, thrombocytopenia
More immature myeloid cells leads to less mature RBC, neutrophils, platelets, etc.
What cells of the myeloid lineage would be present in the peripheral blood smear for CML?
Myeloblasts, myelocytes, metamyelocytes (precursor cells of the myeloid lineage)