CML ICD Flashcards
What are the four types of myeloid cells?
Neutrophils, Monocytes, Eosinophils, and Basophils
What are the three types of lymphoid cells?
B, T, and NK Cells
The division of multipotential hematopoetic stem cells into myeloid and lymphoid progenitors
Hematopoiesis
Myeloid progenitor cells differentiate into what 6 things?
Monocytes, neutrophils, eosinophils, basophils, platelets, and erythrocytes
Lymphoid progenitor cells differentiate into
T lymphocytes and B lymphocytes
A myeloproliferative disorder characterized by increased proliferation of the granulocytic lineage cells without the loss of their capacity to differentiate
Chronic Myelogenous Leukemia (CML)
What percentage of all leukemias that occur in adults are CML?
20%
What is the incidence of CML? Is it more common in men or women?
1-1.5/100,000
More common in men
CML most commonly affects adults in
Middle Age
Characterized by fatigue (34%), weightloss (20%), and early satiety
-often discovered incidentally by complete blood cell count (CBC)
CML
What physical characteristic was noted (historically) on >90% of CML patients at diagnosis?
Splenomegaly
Abnormal enlargement of the spleen
-The most common physical finding in patients with CML
Splenomegaly
Spleen size correlates with the
Peripheral blood granulocyte counts
Alterations in hematopoeitic stem cells causes them to leave the bone marrow and take up residence in the spleen, leading to
Extramedullary Hematopoiesis
Production of blood cells components OUTSIDE of the bone marrow
Extramedullary Hematopoiesis
In the 1960’s, Nowell and Hungerford identified aminute chromosome associated with
CML
A small version of chromosome 22 that appears to have a MUCH smaller long arm
-characteristic of CML
Philadelphia Chromosome
In 1973, Dr. Jane Rowley determined that the Philadelphia Chromosome was generated by a
Balanced (reciprocal) Translocation between chromosomes 9 and 22
With balanced translocations, the individual is often
Phenotypically normal
If CML is a balanced translocation, then why are these patients NOT phenotypically normal?
The balanced translocation creates a chimeric protein
What is the name of the chimeric protein generated in the balanced translocation characteristic of CML?
BCR-ABL protein
A tyrosine kinase that promotes growth and survival
c-Abl
c-Abl helps to regulate the
DNA damage repair response
This proteins activity is very tightly regulated
c-Abl
Gains a domain from BCR that facilitates dimerization
c-Abl
c-Abl gains a domain from BCR that facilitates
Dimerization
Whe compared to c-Abl, Bcr-Abl is
Constitutively active
The constitutively active Bcr-Abl, then continuously activates
Ras, STAT, an AKT
c-Abl is normally located in the
Nucleus
Bcr-Abl however is trapped in the
Cytoplasm
Drives growth and formation of myeloid progenitors
Bcr-Abl
Characterized by proliferation of excess myeloid progenitor cells and increased WBC count
-Less severe portion of CML
Chronic Phase
The most severe portion of CML characterized by excess massive myeloid and lymphoid progenitors that will no longer differentiate
-leads to death
Blast Crisis
Bcr-Abl location in the cytoplasm alters the
DNA-damage response
CML was first described by
John Hughes Bennet, MD
What are two forms of molecular diagnostics in CML?
- ) Cytogenic analysis
2. ) FISH
Can confirm the presence of the Bcr-Abl protein
RT-PCR
A unique family of non-receptor protein-tyrosine kinases that are highly conserved
c-Able (Ableson gene) proteins
In the Bcr-Abl fusion protein, there is a GAIN-OF-FUNCTION for the Abl tyrosine kinase such that is is
Constitutionally active
What does Bcr stand for?
Breakpoint cluster region
A drug that blocks ATP binding to Bcr-Abl and prevents the activity of the chimeric protein
Imatonib
