Leukaemia (AML, ALL, CML, CLL) Flashcards
What are acute leukaemias?
- Neoplastic conditions with rapid onset
- Characterised by the presence of immature cells (blasts) in the blood and bone marrow
What are the clinical effects of acute leukaemias?
They cause bone marrow failure:
- Anaemia (↓ Hb): fatigue, pallor, breathlessness
- Neutropenia (↓ neutrophils): recurrent infections
- Thrombocytopenia (↓ platelets): bleeding and easy bruising
Describe how a blood stem cell splits.

What is the best investigation for differentiating lymphoid from myeloid leukaemias?
Immunophenotyping - shows antigens
What is the pathogenesis of acute myeloid leukaemia? What causes it?
Defect in the step which converts blast cell (myeloblast) to granulocytes (eosinophils, basophils, neutrophils). There is clonal explansion of myeloid blast cells in bone marrow, peripheral blood or extra-medullary tissues.
Aetiology: unknown
What investigations are used for diagnosing leukaemias?
Cytogenetic analysis
FISH - chromosome translocations identified
Molecular genetic analysis
Immunophenotyping
Histology
What is the management of AML?
Supportive e.g. RBC, plt, FFP, abx, allopurinol
Chemotherapy
Targeted molecular therapy
Transplantation
What are the risk factors for AML?
- Down’s
- Irradiation
- Anti-cancer drugs
- Age (incidence increases with age)
Common in the elderly population.
What are the clinical features of AML? How do you diagnose it?
- Bone marrow failure - bleeding, infections, anaemia, hyperviscosity
- Splenomegaly, hepatomegaly
- Gum infiltration
- Skin/CNS palsies
- Lymphadenopathy
Diagnosis: Auer rods on blood film, myeloblast cells (10-19%)

What is promyelocytic leukaemia?
An AGGRESSIVE subtype of AML
aka APML
What is the cause of promyelocytic leukaemia? What is a common complication?
t(15;17)
Associated with DIC
What is the pathogenesis of acute lymphoblastic leukaemia?
- Defect is in the lymphoblast to B/T/NK cell pathway.
- –> uncontrolled proliferation of lymphoblasts
- 3/4 are B cell ALL (acute lymphoblastic leukaemia)
What are the clinical features of ALL?
- Child - 75% under 6 years old
- Bone marrow failure - anaemia, infection, bleeding
- Lymphadenopathy
- Splenomegaly, hepatomegaly
- Sanctuary sites - testes and CNS
- Thymic enlargement → stridor
What are the histological features of ALL?
- Bloods: high WCC, low Hb, low Plt
- Bone marrow film: >20% lymphoblasts
What is the management of ALL?
- Systemic 2-3yrs of therapy (boys treated longer as lymphoblasts accumulate in testes) e.g. imatinib for Ph+ve
- CNS-specific therapy (all patients)
What is the pathogenesis of chronic lymphocytic leukaemia?
Accumulation of mature incompetent lymphocytes (unable to undergo apoptosis) that are able to self-renew. So bone marrow becomes infiltrated.
What are the histological features of CLL? What other investigation can be done?
- Cells are fragile –> break when smeared on a blood film–> smear/smudge cells
- Bloods - ↑ lymphocytes, ↓ Hb, ↓ neutrophils, ↓ platelets
Flow cytometry is useful
Most diagnosed on FBC for unrelated reason
What mutations may cause CLL to progress to a more aggressive type?
Richter transformation - risk is 1% a year
What are the clinical features of CLL?
Median age 72yrs at diagnosis
Lymphoctyes can infiltrate lymphatic tissues and haemopoietic organs such as liver, spleen and bone marrow
- Lymphadenopathy
- Splenomegaly in 50%
- SOB
- Fatigue
What two syndromes is CLL associated with?
- Can be associated with autoimmune thrombocytopenia + anaemia = Evan’s syndrome
- Can transform to aggressive NHL = Richter’s syndrome
What is the management of CLL?
Supportive - vaccination, prophylactic abx
Immunotherapy - BCR kinase inhibitor (e.g. ibrutinib), BCL2 inhibitors (e.g. venetoclax)
Chemotherapy
Allogeneic SCT
Under what type of lymphoma does CLL fall?
NHL (B cell type) - indolent
What is the pathophysiology of chronic myeloid leukaemia?
Uncontrolled proliferation of granulocyte precursors in BM but slower proliferation than AML (myeloblast to granulocyte step that leads to basophil /eosinophil /neutrophil production)
Malignant clonal disorder of haemopoietic stem cell that results in marked myeloid hyperplasia in the bone marrow. AKA chronic granulocytic leukaemia
When does CML usually present? What is a known risk factor?
Usually presents at age 53
Exposure to ionising radiation is the only known risk factor