Translocations and haem malignancies

Question 1

t(9;22)

Answer 1

Philadelphia chromosome
In over 95% of cases of CML
Results in part of the Abelson proto oncogene being moved to the BCR gene on chromosome 22
The resulting gene encodes for a fusion protein that has tyrosine Kinase activity in excess of normal
POOR prognostic predictor in ALL

Question 2

t (15;17)

Answer 2

APML

Fusion of PML and RAR-alpha genes

Question 3

t(8;14)

Answer 3

Burkitt’s lymphoma

MYC oncogene is translocated to an immunoglobulin gene

Question 4

t(11;14)

Answer 4

Mantle cell lymphoma

Deregulation of cyclin D1 (BCL-1) gene

Question 5

EBV associated with which haemopoietic malignancies?

Answer 5

Hodgkin
Burkitt
PTLD

Question 6

HTLV-1 associated with which haemopoietic malignancies?

Answer 6

Acute T-lymphoblastic leukaemia/lymphoma

Question 7

HIV associated with which haemopoietic malignancies?

Answer 7

Cerebral DLBCL
DLBCL
Hodgkin

Question 8

HHV-6 associated with which haemopoietic malignancies?

Answer 8

Primary effusion lymphoma (often HIV positive also)

Question 9

Which chemos notoriously produce treatment related AML/MDS?

Answer 9

Etoposide
Anthracyclines
Cyclophosphamide
Autologous stem cell transplant

Also Benzene–>myeloma
Also hair dye –>Follicular lymphoma
ALso radiation–>CML/MDS/secondary acute leukaemia

Question 10

Blast with Auer rods think…

What will you see on cytochemistry…

Answer 10

AML

On cytochemistry will see myeloperoxidase positive

Question 11

What are the flow cytometry markers in AML?

Answer 11

CD 13

CD 33

Question 12

Strongest prognostic marker in AML?

Answer 12

Age of patient. Poor over 60

Chemo has not been shown to improve survival

Question 13

Good or bad in AML?

t(15;17)

Answer 13

good

Question 14

Good or bad in AML?

inv(16)

Answer 14

good

and tend to respond well to anthracyclines

Question 15

Good or bad in AML?

t(8;21)

Answer 15

good

and tend to respond well to anthracyclines

Question 16

Good or bad in AML?

normal karyotype

Answer 16

intermediate

Question 17

Good or bad in AML?

del7 and del5q

Answer 17

poor

Question 18

Good or bad in AML?

inv(3)

Answer 18

poor

Question 19

Good or bad in AML?

t(3;3)

Answer 19

poor

Question 20

Good or bad in AML?

t(6;9)

Answer 20

poor

Question 21

Good or bad in AML?

t(9;22)

Answer 21

poor

Question 22

Good or bad in AML?

11q23

Answer 22

poor

Question 23

In normal karyotype leukaemia (which is intermediate risk), what does the Flt3 receptor mutation and NPM1 mutation mean?

Answer 23

Molecular markers
Flt3 ITD receptor mutation - poor
NPM1 mutation - good

Question 24

Acute lymphoblastic leukaemia morphology:

Answer 24

Acute leukaemia with more than 20% blasts in blood or bone marrow
NO Auer rods

Question 25

Immunophenotyping for ALL?

Answer 25

Lymphoid antigens: CD10 TdT B cell CD 19 CD20 T cell CD 2 CD3 CD 4 CD8

Question 26

Good or bad cytogenetics in ALL? | t(9;22)

Answer 26

poor

Question 27

Good or bad molecular mutation profile in ALL? | Bcr-Abl

Answer 27

poor still incurable with chemo without transplant Do give inhibitor eg imatinib dasatinib give allogeneic transplant to these people in first clinical remission, or other ALLs if have relapsed disease.

Question 28

List bad in aml

Answer 28

-5 -7 Del 5q 5 or more unrelated abn 3q abnormality

Question 29

Good in aml

Answer 29

T 15 ;17 T 8;21 Inv 16

Question 30

What is the role of cytogenetics for AML first up?

Answer 30

Can change management strategy. Ie do you go for allo SCT as up front therapy or not.

Question 31

Do you give maintenance in acute leukaemias?

Answer 31

ALL yes 2 years | AML no

Question 32

Immunophenotyping in CLL

Answer 32

CD5 CD19 B cells that show clonality ie kappa or lambda light chain restricted

Question 33

Favourable cytogenetics in CLL?

Answer 33

13q deletion

Question 34

Poor cytogenetics in CLL?

Answer 34

11q | 17p

Question 35

CLL gold standard chemo

Answer 35

Fludarabine Cyclophosphamide Ritux

Question 36

Treatment for MDS with 5q del?

Answer 36

Lenalidomide

Question 37

How to tell the difference between chronic phase, accelerated phase and blast crisis in CML

Answer 37

Chronc under 15% blasts Accel 15-29% Crisis 30 or more plus other factors can bump up

Question 38

In JAK2 negative MF and ET, what mutation could you see?

Answer 38

Calreticulin!!!! Usually doesn't coexist with JAK2 A "good" mutation