Slides 11-25

Chronic Myelogenous Leukemia (CML)

AKA Chronic ​ (a)   leukemia

​ (b)   - First described

1960 - First malignancy associated with a consistent ​ (c)   – ​ (d)   – diagnostic cytogenetics

• granulocytic
• 1845
• genetic defect
• “Philadelphia chromosome”

Match the following

• BCR/ABL = abnormal gene fusion/oncogene

• Molecular diagnostics

• new, smaller CHR 22

• Phases of Chronic CML

• symptomatic, hyperproliferative stage; spillover from BM: 10-19% blasts; increase in basophils

• Accelerated phases of CML

• PCR for BCR/ABL to test for genetic defect and determine minimum residual disease (MRD)

• t(9;22) makes Ph¹ =

• asymptomatic, proliferative stage; no physical symptoms; <10% blasts in BM

• Philadelphia chromosome (Ph¹)

Reorder the following events

• Has gene fusion called BCR/ABL, an oncogene

• New CHR22 is called the Philadelphia chromosome, Ph¹

• BCR/ABL translated into abnormal tyrosine kinase enzyme

• Increased cell proliferation, decreased apoptosis of granulocytes

• DNA in CHR 9 and 22 breaks, translocates

  Forms new "versions of CHR 9 and CHR 22

Phases of CML (cont.)

​ (a)   : “blast crisis,” blasts accumulate, ​ (b)   , bleeding, 20%+ blasts

May ​ (c)   accelerated phase

​ (d)   after blastic phase; may be ​ (e)   to treatment

• Acute/Blastic
• sepsis
• skip
• Poor prognosis
• unresponsive
• Chronic Blastic
• responsive
• Good prognosis

Choose all of the clinical features unique to Chloromas (CML).

• brownish tumors, due to MPO presence

• infiltration of extramedullary sites with myeloid cells (spleen, liver)

• greenish tumors, due to MPO presence

• fades to "dirty yellow" upon exposure to air

Match the following CML lab findings.

• No leukemic hiatus

• Leukocytosis

• >100,000 cells/µL; all stages of maturity; cells spill over from BM into PB

• Increased PLT

• basophils and eosinophils

• Myelocytic bulge

• typically a precursor of more myelocyte than any other stage

• In PB or BM

• usually <20% unless blast crisis

• Blasts and pros

In CML lab findings Anemia is normocytic and/or normochromic.

• True

• False, just normocytic

• False, just normochromic

CML lab findings (cont.)

​ (a)   or ​ (b)   LAP (leukocyte alkaline phosphatase) activity

Visualization of​ (c)   by cytogenetics and ​ (d)  

Detection of BCR/ABL by PCR

›Establishes ​ (e)  

›Monitors MRD

›5% are negative (aCML) – poor prognosis

• Low
• no
• t(9;22)
• FISH
• baseline
• t(15;23)
• prognosis
• High
• many

CML lab findings (cont.)

Low​ or ​ no ​ (a)   (leukocyte alkaline phosphatase) activity

Visualization t(9;22) of​ by ​ (b)   and ​ FISH

Detection of ​ (c)   by PCR

›Establishes ​baseline

›Monitors ​ (d)  

​ (e)   (aCML) – poor prognosis

• LAP
• cytogenetics
• BCR/ABL
• MRD
• ›5% are negative
• >5% are positive
• MRS
• generations

Match the following CML treatments.

• reducing white cell

• Prognosis

• not super effective

• Hydroxyurea

• boe marrow

• Leukapheresis

• can achieve remission if responsive to TKI

  Poor if BCR/ABL negative

• Tyrosine Kinase Inhibitors (TKI)

• Gleevec (imatinib) -WOO!

  $$$$ - BOO!

• transplant