CML Module--Krafts Flashcards
CML
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
cell predominance
neutrophils
RBCs
megakaryocytes
all lines–fibrosis of marrow
What type of enzyme is normally mutated in chromic myloproliferative disorders?
tyrosine kinases
What is the odd thing you see on a slide in CML?
basophilia
What is the only cause of basophilia?
chronic myeloid leukemia
(CML)
Basic lab findings of CML
- high WBC
- neutrophilia with left shift
- basophila
- anemia
- high platelets (at first)
-decreased leukocyte alkaline phosphatase (LAP)
LAP only in neutrophils
Leukocyte alkaline phosphatase
(LAP)
seen only in neutrophils
decreased in malignancy
What is the mutation in CML?
Philedelphia chromosome
t(9;22)
What does the spleen do in CML?
extramedullary hematopoiesis
Chronic phase CML
- stable counts
- easily controlled
- 3-4 years (untreated)
- becomes either accelerated phase or blast crisis
Accelerated phase CML
- unstable counts
- blast crisis within 6-12 mo.
- 50% of patients with chronic phase CML
Blast crisis
- acute leukemia
- high mortality
- 50% of patients from chronic phase CML
Chronic phase
Accelerated phase
Blast crisis
in CML
chronic phase is stable
50% become accelerated phase
50% become blast crisis
How can you get an acute lymphoblastic leukemia from CML?
blast crisis
t(9;22) occurs high up in progenitor cells
3 types of CML remission
hematologic remission: nomal CBC and physical
cytogenetic remission: no t(9;22) on metaphases
molecular remission: no BCR/ABL transcripts by PCR
Mutation in polycythemia vera
Jak-2 mutation
JAK = just another kinase
EPO in polycythemia vera
low
problem is in progenitor cells
Pruritis in polycythemia vera
due to basophils
(and that’s all we know)
Pathway disrupted in polycythemia vera
JAK-STAT pathway
mutated JAK-2
constitutively activated
STAT = signal transducer and activator of transcription
Tx of polycythemia vera
phelbotomy
maybe myelosuppressive drugs?
Survival in polycythemia vera
9-14 years
death from hemorrhage or thrombosis
Essential thrombocythemia odd population
young women (~30 y/o)
Why do you look for the Philedelphia chromosome in thrombocythemia?
need to rule out CML
CML can cause high platelet counts
essential thrombocythemia is a Dx of exclusion
Chronic myelofibrosis cell line
panmyelosis
all cell lines
What type of cell is seen predominently in chronic mylofibrosis?
teardrop red cells
chronic myelofibrosis
Pathophys of chronic myelofibrosis
filling up marrow
extramedullary hematopoiesis
Ph’
Philedelphia chromosome
t(9;22) translocation makes what fusion protein?
BCR-ABL1 tyrosine kinase
What drug binds BCR-ABL1 ATP binding site?
imatinib
Imatinib MOA
selectively binds BCR-ABL1 fusion protein tyrosine kinase ATP binding site
Function of myristate on ABL1
autoinhibition of ABL1 tyrosine kinase
