Translocations and haem malignancies Flashcards
t(9;22)
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
t (15;17)
APML
Fusion of PML and RAR-alpha genes
t(8;14)
Burkitt’s lymphoma
MYC oncogene is translocated to an immunoglobulin gene
t(11;14)
Mantle cell lymphoma
Deregulation of cyclin D1 (BCL-1) gene
EBV associated with which haemopoietic malignancies?
Hodgkin
Burkitt
PTLD
HTLV-1 associated with which haemopoietic malignancies?
Acute T-lymphoblastic leukaemia/lymphoma
HIV associated with which haemopoietic malignancies?
Cerebral DLBCL
DLBCL
Hodgkin
HHV-6 associated with which haemopoietic malignancies?
Primary effusion lymphoma (often HIV positive also)
Which chemos notoriously produce treatment related AML/MDS?
Etoposide
Anthracyclines
Cyclophosphamide
Autologous stem cell transplant
Also Benzene–>myeloma
Also hair dye –>Follicular lymphoma
ALso radiation–>CML/MDS/secondary acute leukaemia
Blast with Auer rods think…
What will you see on cytochemistry…
AML
On cytochemistry will see myeloperoxidase positive
What are the flow cytometry markers in AML?
CD 13
CD 33
Strongest prognostic marker in AML?
Age of patient. Poor over 60
Chemo has not been shown to improve survival
Good or bad in AML?
t(15;17)
good
Good or bad in AML?
inv(16)
good
and tend to respond well to anthracyclines
Good or bad in AML?
t(8;21)
good
and tend to respond well to anthracyclines
Good or bad in AML?
normal karyotype
intermediate
Good or bad in AML?
del7 and del5q
poor
Good or bad in AML?
inv(3)
poor
Good or bad in AML?
t(3;3)
poor
Good or bad in AML?
t(6;9)
poor
Good or bad in AML?
t(9;22)
poor
Good or bad in AML?
11q23
poor
In normal karyotype leukaemia (which is intermediate risk), what does the Flt3 receptor mutation and NPM1 mutation mean?
Molecular markers
Flt3 ITD receptor mutation - poor
NPM1 mutation - good
Acute lymphoblastic leukaemia morphology:
Acute leukaemia with more than 20% blasts in blood or bone marrow
NO Auer rods
Immunophenotyping for ALL?
Lymphoid antigens:
CD10 TdT
B cell CD 19 CD20
T cell CD 2 CD3 CD 4 CD8
Good or bad cytogenetics in ALL?
t(9;22)
poor
Good or bad molecular mutation profile in ALL?
Bcr-Abl
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.
List bad in aml
-5
-7
Del 5q
5 or more unrelated abn
3q abnormality
Good in aml
T 15 ;17
T 8;21
Inv 16
What is the role of cytogenetics for AML first up?
Can change management strategy. Ie do you go for allo SCT as up front therapy or not.
Do you give maintenance in acute leukaemias?
ALL yes 2 years
AML no
Immunophenotyping in CLL
CD5 CD19 B cells that show clonality ie kappa or lambda light chain restricted
Favourable cytogenetics in CLL?
13q deletion
Poor cytogenetics in CLL?
11q
17p
CLL gold standard chemo
Fludarabine
Cyclophosphamide
Ritux
Treatment for MDS with 5q del?
Lenalidomide
How to tell the difference between chronic phase, accelerated phase and blast crisis in CML
Chronc under 15% blasts
Accel 15-29%
Crisis 30 or more
plus other factors can bump up
In JAK2 negative MF and ET, what mutation could you see?
Calreticulin!!!!
Usually doesn’t coexist with JAK2
A “good” mutation
