CML Flashcards
1
Q
Chronic Myelogenous Leukemia is what kind of disorder?
A
- myeloproliferative
- characterized by increased proliferation of the granulocytic lineage cells without the loss of their ability to divide
2
Q
Key features of CML in patient history:
A
- incident discovery by CBC
- fatigue
- weight loss
- easy bruising
- low grade fevers
3
Q
Key features of CML in patient blood work:
A
- elevated WBC
4
Q
Which WBCs are normally elevated in CML?
A
- neutrophils and lymphocytes
5
Q
Key features of CML in patient physical exam:
A
- normal
- pallor (paleness)
- splenomegaly (enlarged spleen)
6
Q
Why do some patients present with an enlarged spleen in CML?
A
- Alterations in hematopoeitic stem cells and their interactions with the bone marrow stem cell niche allow abnormal progenitor trafficking.
- Abnormal cells take up residence in the spleen and proliferate.
7
Q
CML is caused by:
A
- a chromosomal disorder
- balanced reciprocal translocation between chromosomes 9 and 22 (no loss of genetic information)
- “Philadelphia Chromosome”
8
Q
Breakpoints for the balanced reciprocal translocation that gives rise to CML are located where?
A
- within the intron regions of the BCR gene of chromosome 22 and the intron regions of the Abl gene on chromosome 9.
9
Q
How does the balanced reciprocal translocation give rise to CML?
A
- Abl is a cytoplasmic tyrosine kinase normally inhibited by a region of itself.
- Inhibitory region is lost in translocation, and Abl gains a domain from BCR that facilitates dimerization of BCR-Abl with another BCR-Abl.
- Leads to a constitutively active Abl.
- No regulation.
10
Q
c-Abl is:
A
- a nuclear and cytoplasmic tyrosine kinase
11
Q
c-Abl is important for:
A
- cell survival, cell proliferation, DNA repair
12
Q
When compared to c-Abl, BCR-Abl is:
A
- constitutively active.
- trapped primarily in the cytoplasm.
- therefore it is NOT in the nucleus and not able to carry out its DNA repair function.
13
Q
The BCR-Abl mutation first occurs in what type of cell?
A
- hematopoietic stem cells
14
Q
BCR-Abl RT-PCR Banding in Normal Patient:
A
- Single 808 bp fragment in normal WBC
15
Q
BCR-Abl RT-PCR Banding in CML patient:
A
- Single 808 bp fragment PLUS 310 or 385 bp fragment.
16
Q
Which lanes have a BCR-Abl protein indicative of CML?
A
- lanes 3 and 5
18
Q
Imatinib is:
A
- a tyrosine kinase inhibitor (TKI).
- inhibits the binding of ATP to the BCR-Abl tyrosine kinase; tumor cell cannot proliferate and dies.
