ICD CML

Question 1

What is a typical blood workup for a patient with CML?

Answer 1

1. WBC count is very high
2. Hemoglobbin and Hematocrit are lower
3. CBC with differential indicates high percentage of neutrophils and lymphocytes (T-cells especially)

Question 2

Is CML a myeloid of lymphoid expansion?

Answer 2

CML is a myeloid expansion but expansion of lymphocytes can be due to the fact that in general, CML has increased number of precursor and progenitor cells.

Question 3

What is CML?

Answer 3

A myeloproliferative disorder characterized by increasaed proliferation of the granulocytic lineage cells without the loss of their capacity to differenitate.

Question 4

What are the key features of CML in terms of:

• Patient history
• Physical Exam
• Lab results

Answer 4

1. Patient history
   
   1. Discovered through complete blood count (CBC)
   2. Fatigue
   3. Weight loss
   4. Early satiety
   5. Low grade fevers
   6. Excessive sweating
   7. Easy bruising
2. Physical Exam
   
   1. Normal
   2. Spenomegaly (Seen in 90% of patients)
3. Lab results
   
   1. Elevated WBC count

Question 5

How is spleenomegaly linked to CML?

Answer 5

1. Alterations in HSC and their interactions with the bone

marrow environment allow abnormal progenitor

trafficking.

2. Abnormal cells take up residence in the

spleen leading to extramedullary hematopoiesis.

3. *Can also accumulate in liver

Question 6

What chromosomal disorder causes CML?

Answer 6

Chromosome 9 has C-abl and Chromosome 22 has Bcr

• C-abl is a nuclear tyrosine kinase
• Involved in controlling growth, survival, and DNA damage repair response

There is a reciprocal translocation between the long arms of chromosome 9 and chromosome 22 in the hematopoietic stem cell resulting in:

• a changed chromosome 9
• a changed chromsome 22 aka philadelphia chromsomes that has the BCR/ABL fusion.
  
  • creates a BCR/ABL fusion mRNA that creates a BCL/ABL fusion protein
  • Dimerization of the c-ABL is now ligand or growthfactor independent
  • Resuts in contiutively active BCR/ABL such that kinase activity is always on
    
    • Increased proliferation in myeloid compartment
    • Decreased apoptosis in myeloid compartment
    • Genetic instability

Question 7

Molecular diagnostic of CML

Answer 7

1. Normal patient has 808 bp fragment of either BCL or ABL
2. CML patient has 808 bp fragment and 310 or 385 bp fragment
3. RT-PCR can confirm presence of fusion protein
   
   1. In gel, normal patient will just have 808 band
   2. In gel, CML patient will have 808 band and additional band around 300

Question 8

Imatinib aka Gleevec

Answer 8

Imtinib or Gleevec competitively binds to kinase domain site and inhibits Bcr/Abl protein from constitutively phoshorylating substrates.