Flashcards in CML ICD Deck (41):
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
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?
What is the incidence of CML? Is it more common in men or women?
More common in men
CML most commonly affects adults in
Characterized by fatigue (34%), weightloss (20%), and early satiety
-often discovered incidentally by complete blood cell count (CBC)
What physical characteristic was noted (historically) on >90% of CML patients at diagnosis?
Abnormal enlargement of the spleen
-The most common physical finding in patients with CML
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
Production of blood cells components OUTSIDE of the bone marrow
In the 1960's, Nowell and Hungerford identified aminute chromosome associated with
A small version of chromosome 22 that appears to have a MUCH smaller long arm
-characteristic of CML
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
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?
A tyrosine kinase that promotes growth and survival
c-Abl helps to regulate the
DNA damage repair response
This proteins activity is very tightly regulated
Gains a domain from BCR that facilitates dimerization
c-Abl gains a domain from BCR that facilitates
Whe compared to c-Abl, Bcr-Abl is
The constitutively active Bcr-Abl, then continuously activates
Ras, STAT, an AKT
c-Abl is normally located in the
Bcr-Abl however is trapped in the
Drives growth and formation of myeloid progenitors
Characterized by proliferation of excess myeloid progenitor cells and increased WBC count
-Less severe portion of CML
The most severe portion of CML characterized by excess massive myeloid and lymphoid progenitors that will no longer differentiate
-leads to death
Bcr-Abl location in the cytoplasm alters the
CML was first described by
John Hughes Bennet, MD
What are two forms of molecular diagnostics in CML?
1.) Cytogenic analysis
Can confirm the presence of the Bcr-Abl protein
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
What does Bcr stand for?
Breakpoint cluster region