Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FRCPath Genomics > 06 - Leukaemia > Flashcards

06 - Leukaemia Flashcards

1
Q

What is the common cytogenetic rearrangement found in CML

A

t(9;22) - Philadephia chromosome. BCR-ABL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the activity of the fusion protein

A

BCR-ABL has tyrosine kinase activity. the fusion constitutively activates the tyrosine kinase activity to drive cellular proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What treatment options are available in CML

A

> Imatinib can be used in Ph+ CML cases. Recognised as a ‘wonder drug’, can result is complete cytogenetic remission in 80% patients

> Bone Marrow transplant (need suitable donor and is age restricted)

> Interferon alpha - glycoprotein. Induced haematological remission in 70-80% patients, but only complete cytogenetic response in 6-20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the recommended testing pathways for diagnosis and monitoring in CML

A

> Cytogenetic analysis (FISH and karyotype) at diagnosis in Bone Marrow samples.
Continued cytogenetic testing 3-6months on BM.
Routine cytogenetic investigation every 6 months until negative / normal result obtain (CCR - complete cytogenetic remission).
Should analyse 30 metaphases and 100 interphases. >Following this, RT-qPCR is recommended to monitor residual disease and to monitor relapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Patients with CML present with…..

A

> Fatigue (anemia)
weight loss
night sweats
splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the 3 phases of CML

A

1) Chronic phase - 90% of patients diagnosed here (may be asymptomatic and detected via routine blood test) Blasts <5%
2) Accelerated phases, inceased WCC, blasts >10%
3) BLAST crisis - >20% Blasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what additional cytogenetic findings may be detected as patient transforms from Accelerated Phase to blast phase

A

> +8 (50%)
i(17q) (35%)
der22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

ALL is considered a _____________ leukaemia

A

childhood - 75% all childhood Leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 2 types of ALL, which is more common

A

B-cell ALL (most common) & T-cell ALL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Precursor B or T cells may form a mass known as a

A

Lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which types of cytogenetic findings are associated with a GOOD prognosis in ALL

A

> B-ALL with hyperdiploidy (>50chr)

> B-ALL with ETV / RUNX1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which types of cytogenetic findings are associated with a BAD prognosis in ALL

A

> B-ALL with BCR-ABL1
B-ALL with MLL rearrangement
B-ALL with near hypodiploid (23-29chr)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What rearrangement is associated with infant B-ALL

A

> 11q23 rearrangement - MLL gene: t(4;11)

note: poor prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the most common translocation in childhood B-ALL associated with a good prognosis

A

t(12;21) - ETV6/RUNX1

note: children like butterflies and running - both GOOD - 12;21 butterfly
RUNX1 - running

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the rearrangement associated with Burkitt Lymphoma

A

t(8;14) MYC / Igh

also
t(8;2) - MYC / IgK
t(8;22) - MYC / IgL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Was is the common rearrangement found in adult onset ALL.

A

t(9;22) BCR/ABL

POOR prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the proportion of T-cell ALL (T-ALL), in ALL

A

15%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is rearrangement is frequently found in T-ALL

A

Rearrangements of the T-Cell receptor gene TCR

19
Q

what is a good prognosis in T-ALL

A

del(1)(p32q32)

20
Q

What rearrangements are associated with a poor prognosis in T-ALL

A

> t(7;10)
t(10;14)
MLL rearrangements
Complex karyotypes

21
Q

What is the common age of onset in T-ALL

A

Teenagers - adolescence

22
Q

What rearrangements are associated with a GOOD prognosis in T-ALL

A

High hyperdiploidy (51-65chr)

23
Q

CLL is considered a disease of the ________

A

elderly

24
Q

What are the distinct clinical phases in CLL

A

1) Pre-malignant monoclonal B-cell lymphocytes
2) Overt CLL
3) transformation into aggressive lymphoma (Richter’s Syndrome)

25
Q

What proportion of CLL patients develop lymphoma

A

5-15%

26
Q

what types of lymphoma are seen in CLL

A

> Diffuse large B-cell lymphoma (Richter Syndrome) - POOR prognosis (1yr survival)
Classical Hodgkin Lymphoma

27
Q

Why can it be difficult to karyotype CLL patients. what is the alternative

A

Cells in CLL are very difficult to divide even with strong mitogens. Often need to use interphase FISH

28
Q

What are the common cytogenetic findings in patients with CLL

A

> del 13q14 - good prognosis
del 11q23 (ATM gene) - poor prognosis
del 17p13 (TP53 gene) - poor prognosis

29
Q

What cytogenetic findings are associated with POOR prognosis in CLL

A

> del 11q23 (ATM gene) - poor prognosis
del 17p13 (TP53 gene) - poor prognosis
t(8;14) - MYC/IgH
t(14;18) - BCL2 / Igh

30
Q

What is the recommended 1st tier testing strategy in CLL referrals

A

FISH for chromosome 13, 11 (ATM gene) and 17 (TP53)

31
Q

what tests can be performed to distinguish between a myeloid of lymphoid leukaemia

A

1) Histology (cell staining)
- Myeloid cells - express myeloperioxidase enzyme, which forms intracellular crystals known as AUER RODS

2) Immunophenotyping
- the marker TdT (DNA polymerase) is found only in nucleus of lymphoid cells

32
Q

How can you distinguish between a B-Cell and a T-Cell leukaemia

A

Cell surface markers:
B-Cell = CD10
T-Cell = CD8

33
Q

Outline haematopoiesis

A

> haematopoetic stem cell can become either a myeloid or lymphoid cell line

> MYELOID cell line include:

  • erythrocytes (red blood cells)
  • thrombocytes (platelets)
  • granulocytes (inc. basophils, neutrophils and eosinophils)
  • monocytes (white blood cells)
  • macrophages

> LYMPHOID cell line include:

  • T lymphocyte
  • B lymphocyte
34
Q

Outline the pathogenic progression of leukaemia

A

> during haematopoesis, progenitor cells mature from blasts into mature cells - i.e. lymphoblasts mature into lymphocytes
genetic abnormalities can occur which disrupt this maturation process, resulting in the cells remaining as undifferentiated immature blast cells.
these cells are not fully functioning as immature, and so useless to the body, but still take up resources.
furthermore, many of the genetic abnormalities also drive cell proliferation and so get increase blast cells in bone marrow
normal cells have to compete for resources and proliferate less well and may even die, due to ‘crowding out’
this can result in the reduction of there normal cells - cytopenia

35
Q

What are the symptoms common to leukaemia?

A

> fatigue due to anaemia
easy bruising / bleeding due to thrombocytopenia
frequent infections due to neutropenia

36
Q

what is the % blast to diagnosis AML

A

20%

37
Q

AML is more common in __________

A

adults

38
Q

AML accounts for ____% of childhood leukaemia

A

20%

39
Q

Acute promyelocytic leukaemia (APML) is associated with which rearrangement? what is particularly important to consider in patients with APML

A

> APML ass. with t(15;17) - PML-RARA (90%)
good prognosis as can be treated using ATRA (all trans retinioc acid - which bings to RARA)
important clinical issue with APML is risk of these immature cells getting into blood stream, settling and forming a clot = Disseminated Intravascular Coagulation (DIC) - serious life threatening condition

40
Q

What are AUER rods?

A

Auer rods are crystallised aggregates of the myeloperoxidase enzyme - found only in myeloid cells and so can help distinguish between myeloid vs lymphoid leukaemia

41
Q

At a molecular level, AML is considered a multistep process, requiring mutations in at least 2 classes. What are those classes and give examples

A

Class 1 - activate signal transduction pathways which confer proliferation
> FLT3 - receptor tyrosine kinase mutated in 1/3 AML
> PTPN11
> RAS, NRAS, KRAS

Class 2 - Transcription Factors
> many class 2 mutations target the Core Binding Factor (CBF) - heterodimer of RUNX1 and CBFB - which are essential for haematopoietic development
42
Q

What is the most commonly mutated gene in cytogenetically normal AML

A

NPM1 (Nucleophosmin 1))

43
Q

what are the 3 most common rearrangements in adult AML according to ELN

A

> t(15;17) - PML-RARA
t(8;21) - RUNX1-RUNX1TI
inv(16)(p13.1q22) - CBFB-MYH11

note: RUNX1 and CBFB key components of the Core Binding Factor (class 2 mutation target)

FRCPath Genomics (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions