ALL

Question 1

ETV6-RUNX1

Answer 1

t(12;21)

ALWAYS FISH because translocation is cryptic

Commonest B-ALL
Good prognosis

Question 2

TCF3-PBX

Answer 2

t(1;19)

Often loss of Chr1, and subsequent duplication (unbalanced)

Intermediate prognosis
Can be Mu positive

Question 3

KMT2A-AFF1

Answer 3

t(4;11)

B-ALL phenotype with aberrant CD5+

Biphenotypic - arises in pluripotent stem cells, so can see lineage switch from ALL to acute monoblastic

100% concordance rate in twin studies - high penetrance

Question 4

Hyperdiploidy

and detection

Answer 4

Detect with FISH (centromeric probes)

Gives childhood peak in developed countries but not LEDCs

Gives best prognosis

Question 5

BCR-ABL1

Answer 5

t(9;22)

Detect by FISH and may need PCR because not all cells have abnormal cytogenetics

Gives middle age peak

Poor prognosis

Question 6

ETV6-RUNX1 pathophysiology

Answer 6

• RUNX1 codes for CBFa
• CBFa binds to DNA via Histone Acetyl Transferase and activates transcription factors for many genes, including tyrosine kinases
• Fusion gene cannot bind to HAT and binds corepressor molecules (Sin3a, NCoR, HDAC) so there is chromatin condensation and repression of transcription
• Heterodimerisation with ETV6 gives further transcriptional inhibition

Question 7

Pathophysiology BCR-ABL1

Answer 7

Constitutively active ABL1 (tyrosine kinase) leads to autophosphorylation and uncontrolled signalling of downstream processes

Question 8

Pathophysiology KMT2A-AFF1

Answer 8

KMT2A encodes a histone-methytransferase which regulates gene expression for haematopoiesis