Leukemias Flashcards
Types of AML (3)
- Myeloblastic
- Monoblastic
- Megakaryoblastic
Difference between acute and chronic leukemias
Acute: very immature, very fast
Chronic: more similar to mature, slow
Diagnosis of AML
Blast cells >20% or genetic anomalies
Causes of AML (3)
- Increase proliferation
- Decrease apoptosis
- Block differentiation
AML age group
> 65 years
10-15% childhood
AML immunophenotype (4)
CD13+ CD33+ CD117+ TdT-
AML clinical features (4)
- Infections: Candida, Pseudomonas
- Normo normo anemia
- Thrombocytopenia + DIC = bleeding = BRUISES (PML)
- Gum hypertrophy
What are Auer rods made of and in which leukemia are they found?
MPO
Myeloid leukemias
AML mutations (3)
t(8:21) —> RUNX1/CBF1b —> block maturation
t(15:17) —> RARa-PML —> interfere with terminal differentiation = PML
FLT3 —> signals that there’s normal growth —> PML
AML mutation with the best prognosis
t(15:17) / PML
What differentiates PML from AML?
***Coagulopaties
Phenotype is arrested differentiation
Best prognosis
Labs in PML
Options: cancer procoagulant, factor V, FDP, fibrinogen, D-dimers, platelets, thrombin
Decreased:
- Fibrinogen
- Factor V
- Platelets
Increased:
- FDP
- D-dimers
- CP
- Thrombin generation
What is the mechanism of coagulopathies in PML? What is the activator called?
HYPERFIBRINOLYSIS
- Increase in degradation products
- Decrease in inhibitors: PAI-1, a2 antiplasmin
Annexin A2 = fibrinolytic activator ANA1
Myelodysplastic syndrome why are they considered “pre-leukemia”?
They only stop maturation, don’t get posterior mutations
Why do myelodysplastic syndromes rarely turn into AML?
Patients die
How to differentiate between AML and MDS?
Blast amount
Normal: 2-3%
MDS: <20%
AML: >20%
ALL age group
CHILDHOOD (3-7)
Which leukemias are Tdt +?
ALL
CLL
Most common ALL mutations (6)
t(9;22) - adult
t(12;21) - kids
MLL rearrangements
Diploidy
Abnormal karyotype
NOTCH signaling
ALL clinical features (blood 3 and organs 6)
- Anemia normo normo
- Neutropenia = infections, fever
- Thrombocytopenia = bruises, purpura
- Tender bones
- Lymphadenopathy
- Hepatosplenomegaly
- Papilloedema
- Meningeal sx
- Rare testicular swelling
ALL labs
Decrease: cells
Increase:
- Uric acid
- LDH
- Ca2+
t(9;22) mutation:
- Leukemia type
- Age group
- Gene
- Prognosis
“Philadelphia gene”
1. ALL
2. Adults
3. BCR-ABL1
4. Poor prognosis
t(12;21) mutation:
- Leukemia type
- Age group
- Gene
- Prognosis
- ALL
- Kids
- TEL-AML1 or ETV6-RUNX1
- Good prognosis
t(8;21) mutation:
- Leukemia type
- Age group
- Gene
- Prognosis
- AML
- Elder
- RUNX1/CBF1b
t(15;17) mutation:
- Leukemia type
- Age group
- Gene
- Prognosis
- PML
- Elder
- RARa-PML
- Best prognosis
T-ALL pathogenesis
NOTCH signaling
EC cleavage mutation —> insert tandem duplications —> IC PEST deletion
Increases rate of cleavage and nuclear translocation
T-ALL 3 T’s
T-ALL
Thymic mass
Teenagers
CLL age group
60-80 years
Male 2:1
CLL effect on B cells
Mature, weak IgM and IgD
Increased production and life span
Decreased apoptosis
CLL clinical features
- Symmetrical node enlargement
- Anemia normo normo or AI hemolysis
- Thrombocytopenia
- Splenomegaly
- Hypogammaglobinemia = immunosuppresion EC
Genetics and CLL
Chromosome abnormalities:
- del 13q = microRNA loss
- del 11q23 = ATM gene
- T21
- 17p structural = p53 gene
Somatic hypermutation: IGVH gene 50% = poor prognosis
NOTCH1
Which leukemia has smudge/fragile cells?
CLL
CLL lab findings
- B cll increased
- Smudge cells
- CD19+ CD5+ CD23+
Why autoimmune disorders can develop from CLL?
Hemolytic anemia
Thrombocytopenia
Neutropenia
Red cell aplasia
In which leukemia are Rai scores used?
CLL
Rai score indications
0 = 12 year survival
IV = < 4 years
What is small lymphocytic lymphoma?
General lympadenopathy with CLL
SLL + mutation = _____
Diffuse B cell lymphoma
What is the Richter transformation?
SLL + mutation = diffuse B cell lymphoma
CML genetics
BCR-ABL1
CML age group
40-60 years, neonates, elderly
Philadelphia chromosome and which leukemias it causes
t(9;22)
ALL
CML
Blasts in CML
<10%
CML clinical findings
- Hypermetabolism
- Massive splenomegaly
- Anemia
- Thrombocytopenia
- GOUT
Labs in CML
- Luekocytosis
- Basophils, neutrophils, and myelocytes in circulation
- Normo normo anemia
- High or low platelets
- Hypercellular marrow
- Increase URIC ACID
Blastic transformation: which leukemia and what it is
CML
> 20% blases in a matter of days-weeks
Hard to control
Survival is rare if they stay for a few months
Tx: imatinib only temporary
- Protein kinase inhibitor replaces ATP in BCR-ABL1 kinase
CML phases (3)
Chronic = fever & abdominal fullness
<10% blasts
Accelerated = bleeding & opportunists
10-19% blasts
Blast crisis = bone pain
>20% blasts
3 main myeloproliferative disorders
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis
Mechanism of myeloproliferative disorders
TK mutation —> activates without growth factor
What leukemia can myeloproliferative disorders turn into?
AML
Main mutation in myeloproliferative disorders
JAK2
Clinical features of myeloproliferative disorders
- Facial plethora
- Conjunctival suffusion
- Splenomegaly
- Myelofibrosis
What is polycythemia vera?
Increase in everything
*** Hb and RBC volume
Clinical findings of polycythemia vera
- Hyperviscosity
- Hypervolemia
- Hypermetabolism
- Headache, dyspnea, blurry vision, night sweats
- Pruritus after hot bath
- Retinal venous engorgement
- Splenomegaly 75%
- Hemorrhage or thrombosis
GOUT
What is essential thrombocythemia?
> 450,000 platelets for > 2 months
Thrombosis in head, hands, feed
Bleeding in nose, bruising
Splenomegaly
Tx: aspirin, hydroxyurea, IFNa, plateletpheresis
Polycythemia vera treatment
Phlebotomy
Hydroxyurea
IFNa
What is primary myelofibrosis?
Losing architecture in the bone marrow
Hepatosplenomegaly
HSC are surrounded by fibrous and IC substance
