ALL and CLL

Question 1

Does ALL commonly involve B or T cells?

Answer 1

Predominantly B cells

Question 2

In what age group is ALL commonly seen?

Answer 2

Children under the age of ten

Question 3

Is the ALL outcome more or less favourable in children compared to adults?

Answer 3

• More favourable in children

- children who are diagnosed early respond well

Question 4

What cytogenetic risk group(s) give a good prognosis in Acute Lymphoblastic Leukaemia (ALL)?

Answer 4

• High hyperdiploidy (51-65 chromosomes)

- ETV6-RUNX1 (t(12;21))

Question 5

What are the high risk cytogenetics (i.e. those with a poor prognosis) involved with ALL?

Answer 5

• intrachromosomal amplification of chr21 (iAMP21)
• Philadelphia chr: t(9;22)
• MLL rearrangements (e.g. t(4;11))
• Near haploidy (less than 30chr)
• low hypoploidy (30-39 chr)
• near triploidy (60-78 chr)
• complex karyotype

Question 6

Provide details on use of ETV6-RUNX1 FISH probe to detect t(12;21) in ALL

Answer 6

• Probe covers ETV6 (chr12; green signal) and RUNX1 (chr21; red signal)
• Normal interphase signal pattern would be 2R2G
• Positive = 2 red/1 green/1 fusion = one normal copy of RUNX1 on 21q (one red), other red separated into two parts, one translocated onto der12 (one small red) and the other in the ETV6-RUNX1 fusion on der21. Also have one normal copy of ETV6 on 12p (one green)

Question 7

Provide details on use of ETV6-RUNX1 FISH probe to detect high hyperdiploidy in ALL

Answer 7

• 51-65chr instead of 46
• Usually contains additional copies of chr21 therefore when this probe is used you get additional signals from extra chr21
• e.g. 4R2G signal pattern = two normal copies of ETV6 on chr12 and four normal copies of RUNX1 on chr21, confirming +21,+21 part of the karyotype

Question 7

What cytogenetic abnormality is present in around 25% of ALL cases?

Answer 7

• t(12;21)
• marker of favourable outcome
• Detected by FISH as would be cryptic on g-banding

Question 8

Provide details on use of ETV6-RUNX1 FISH probe to detect iAMP21 in ALL

Answer 8

• Consistently show five or more RUNX1 signals by FISH corresponding to 3 or more extra copies of RUNX1 on single abnormal chr21
• Signal pattern = cluster of red signals for iAMP21, one red for normal copy of chr21 and two green for two normal copies of chr12

Question 9

What is the difference in FISH signal patterns observed when using ETV-RUNX1 probe in:

1. t(12;21)
2. High hyperdiploidy
3. iAMP21

Answer 9

1. 2 red, 1 green, 1 fusion
2. 4 red, 2 green
3. 2 green, 1 normal red, 1 amplified cluster of reds

Question 10

Why is it crucial to distinguish between findings for ETV6-RUNX1 probe?

Answer 10

Because even though the FISH nomenclature can look similar the outcomes are so different:

• t(12;21)/high hyperdiploidy = good outcome
• iAMP21 = poor outcome

Question 11

What age group is CLL more commonly seen in?

Answer 11

The older generation

Question 12

In which population is CLL rare?

Answer 12

• Asian population

Question 13

Of the various chromosomal anomalies seen in CLL, which is the most detrimental?

Answer 13

Deletion of 17p or mutation of the P53 gene

Question 14

Other than del 17p or P53 mut, name three other prognostic markers in CLL

Answer 14

• Del 13q14 (favourable outcome)
• Trisomy 12 (intermediate outcome)
• Deletion of segment of ATM gene on chr11 (poor outcome)

Question 15

Around 50% of CLL patients have evidence of what?

Answer 15

Somatic hypermutation in their IGH genes

Question 16

It is thought that the absence or presence of somatic hypermutation represents what in CLL?

Answer 16

Pre or post germinal centre CLL cell transformation, respectively

Question 17

Do patients harbouring a CLL clone that has undergone somatic hypermutation tend to do better or worse than those whose clone has limited or no hypermutation in the IGH genes?

Answer 17

Better

Question 18

What is a rare subtype of CLL?

Answer 18

Hairy cell leukaemia

Question 19

Provide some details on the established familial link in CLL

Answer 19

• Individuals with first degree relatives suffering with CLL have a 2-7 fold increase of being diagnosed