Haematology 10: CML And Myeloproliferative Disorders Flashcards
What is the difference between relative (pseudo) and true Polycythaemia ?
Relative: low plasma volume, normal Hb, high haematocrit
True: normal plasma volume, high Hb, high haematocrit
List 4 myeloproliferative disorders ?
Polycythaemia Vera
Essential thrombocytopenia
Primary myelofibrosis
CML
If a person has 18% myeloblasts do they have
A) MDS
B) CML
C) ALL
D) AML
A)-MDS
MDS is 5-19% blasts
AML is 20% + blasts
CML has fully differentiated but overproduced Myelocytes
ALL is lymphocytic not myeloid
What is the physiological role of Tyrosine kinases ?
Phosphorylate genes that cause cell growth (increased myeloid cell production)
They do not affect differentiation just proliferation
Which gene is most commonly mutated in polycythaemia rubra Vera ?
JAK2
What affect does JAK2 mutation have on erythropoeisis ?
JAK2 normally phosphorylates EPO receptors in response to EPO.
When mutated this process is constitutively activated so erythropoiesis occurs without regulation by EPO
What is the most pathognomonic sign/symptom of polycythaemia rubra Vera ?
Aquatic pruritus- hot baths causing itching
Give 2 treatments of polycythaemia rubra Vera ?
Hydroxycarbamide
Venesection
Which leukaemia is associated with massive Splenomegaly and hepatomegaly ?
CML
What are the 3 phases of CML ?
Chronic phase
Accelerated phase
Blast crisis
What is the most common chromosomal abnormality in CML ?
t(9;22)- BCR-ABL
Philadelphia chromosome
Which modality is useful for monitoring treatment response in CML ?
RT-PCR (reverse transcriptase)
What is the 1st line treatment for CML ?
Imatinib (tyrosine kinase inhibitor)
Which test allows you to tell the difference between reactive neutrophilia and leukaemia neutrophilia (CML) ?
Leukocyte alkaline phosphatase
Low in CML
Normal/ High in reactive neutrophilia
list appropriate causes of raised erythropoietin
high altitude
hypoxic lung disease
cyanotic heart disease
high-affinity haemoglobin
list Philadelphia negative myeloproliferative neoplasms
PV
ET (essential thrombocytopaenia)
PMF (primary myelofibrosis)
list different myeloid malignancies
AML
Myelodysplasia
Myeloproliferative disorders
CML
list different lymphoid malignancies
precursor cell malignancy eg ALL (B and T cell)
mature cell malignancy eg CLL, MM, lymphoma (H+ NH)
what does a mutation in TK genes result in
expansion of mature cells
what mutations are associated with myeloproliferative disorders
JAK 2 (V617F) - PV (100%), ET, PMF
Calreticulin - ET and PMF
MPL - ET
symptoms of PV
hyperviscocity:
- headaches, light headedness, stroke, visual dist, fatigue, dyspnoea
increased histamine release:
- aquagenic pruritus, peptic ulceration
symptoms of ET
bimodal (30, 55)
incidental finding in 50%
thrombosis:
- CVA, gangrene, TIA, DVT, PE
bleeding:
- mucous membranes and cutaneous
treatment for ET
aspirin
hydroxycarbamide (antimetabolite that suppresses cell turnover)
anagrelide (inh pl but rarely used)
prognosis for ET
normal life span in many
leukaemic transformation in 5% over 10 yrs
myelofibrosis uncommon
define myelofibrosis
clonal myeloproliferative disease associated with reactive BM fibrosis
extra medullary haematopoiesis
60-70 yrs
symptoms of myelofibrosis
cytopaenias thrombosis splenomegaly (MASSIVE) hepatomegaly hypermetabolic state (B symptoms + hyperuricaemia)
signs of myelofibrosis
leukoerythroblastic tear drop poikilocytes giant platelets circulating megakaryocytes dry tap BM trephine biopsy - increased reticulin or collagen fibrosis spleen - intramedullary hematopoiesis
JAK 2/ CALR mutation
treatment for myelofibrosis
supportive - RBC and pl transfusion cytoreductive therapy - hydroxycarbamide ruxolitinib - JAK2 inhibitor allogenic SC transplantation splenectomy
features of CML
more common in M
40-60 yrs
radiation exposure = RF
chronic phase (5-6 yrs) - accelerated (6-12 m) - blast crisis (3-6m)
PHILADELPHIA CHROMOSOME - 22q, Bcr-abl, codes for a tyrosine kinase
presentation of CML
lethargy hypermetabolism thrombotic event mono-ocular blindness CVA bruising bleeding MASSIVE splenomegaly /hepatomegaly
massive leukocytosis
Hb and pl normal/ raised
blood film:
neutrophils, myelocytes not blasts, basophilia
treatment for CML
1st gen tyrosine kinase inhibitor
- Imatinib
2nd gen
- Dasatinib, Nilotinib
3rd gen
- Bosutinib
Allogenic SC transplant
