14: Leukemia

Question 1

Define leukemia

Answer 1

Cancer of the blood that usually originates in bone marrow, results in abnormally high blood cells

Question 2

Epidemiology?

Answer 2

5% of all cancers

Most common in age 15-24

Question 3

Types of leukemia?

Answer 3

ALL - acute lymphoblastic
AML - acute myeloid
CLL - chronic lymphocytic
CML - chronic myeloid

Question 4

How does it occur?

Answer 4

Multiple mutations in a single haemopoietic/lymphoid stem cell giving rise to CLONES that replace normal cells

Question 5

Difference between acute and chronic myeloid leukemia?

Answer 5

AML - mutation affects TFs, so transcription of multiple genes affected. FAILURE of production of end cells

CML - mutation affects a protein in cell signalling pathway between surface receptor and nucleus.
Cell function not affected as much as AML, but cell becomes independent of external signals and there is increased proliferation and survival
INCREASED production of end cells

Question 6

Difference between acute and chronic lymphoid leukemia?

Answer 6

ALL - INCREASE in lymphoblasts (immature) cells. These fail to develop into B/T cells

CLL- MATURE but ABNORMAL B/T cells

Question 7

How does leukemia cause its symptoms

Answer 7

• Metabolic effect of leukemic cell proliferation (weight loss, renal failure, hyperuricaemia)
• Loss of immune function due to loss of normal B/T cells (seen in CLL)

Question 8

Haematological features of ALL

Answer 8

Leucocytosis + lymphoblasts present
Lymphoblasts -> high nuclear-cytoplasmic ratio, nucleoli may be seen as well
Normocytic + normochromic anaemia
Neutropenia
Thrombocytopenia
Bone marrow cells replaced by lymphoblasts

Question 9

Immunophenotyping of ALL?

Answer 9

CD10 - common ALL antigen in B-lineage

TDT - tells you cells are immature (i.e. lymphoblasts)

Question 10

Cytogenetic analysis of ALL

Answer 10

Hyperdiploidy - good prognosis

Translocation - bad prognosis

Question 11

General mechanisms of leukemia, and ALL in particular

Answer 11

Translocation, forming a fusion gene
Dysregulation of proto-oncogene by being close to a promoter gene (common in T-lineage)
Point mutation in proto-oncogene

ALL is a result of mutation in T or B-lineage lymphoid stem cell

Molecular genetic events determine phenotype and prognosis of disease

Question 12

Cytogenetics of ALL?

Answer 12

Translocation of genes on chromsome 12 and 21

Leading to fusion gene ETV6-RUNX1

Question 13

What technique do we use to assess cytogenetics?

Answer 13

FISH (flourescence in situ hybridisation)
ETV6 = green probe
RUNX1 = red probe
if they fuse they turn yellow

Question 14

Example of dysregulation of proto-oncogene?

Answer 14

TCL3 gene disregulated by proximity to TCRA gene

Question 15

Treatment for ALL?

Answer 15

Anaemia -> red cell transfusion
Thrombocytopenia -> platelet transfusion
Antibiotics for infection
Systemic chemo
Intrathecal chemo