week 19 p2

Question 1

What is hematologic malignancy

Answer 1

Involves abnormal productions of blood cells and immune cells eg leukaemia and lymphoma

Question 2

Why is genetic defects in HM important

Answer 2

· Many subtypes of acute and chronic leukaemia’s are linked with DNA changes

· Genetic lesions can be used as diagnosis ad prognosis

Also may lead to improvement in threptic approach using molecular defects

Question 3

How is the overall survival in Acute myeloid leukaemia measured

Answer 3

· Detection of chromosomal abnormalities by cytogenetic analysis is important in diagnosis

Question 4

What is the detection of AML in chromosome

Answer 4

Detection of (8;21) (5;17) (q22;q22,1)

Question 5

What are the types of genetic lesions in HM

Answer 5

· Translocations that result in abnormal gene expression

· due to placement of genes near enhancer or promoter element of other genes

· Translocations that produce chimeric fusions proteins (proteins that create joining of two or more genes that originally for same or separate proteins) with biological activity

Mutations is known oncogenes/tumour suppressor genes

Question 6

What is the consequences of translocation

Answer 6

· The immunoglobin gene (B cells is in the immunoglobin in the cell surface)

· Causes abnormal or altered expression of the normal protein produced by other gene

It is the abnormal expression, timing an levels are inked with malignant phenotype

Question 7

How does the chromosomal translocation link to neoplasm(abnormal growth in cells)
give eg

Answer 7

· Follicular lymphoma, t(14;18), IgH-bcl-2 causes inhibition of apoptosis cyclin ( so cells do not die)

· Burkitt’s lymphoma, t(8;14), IgH,myc cause transcription factors

CML, t(9;22), bcr-abl causes tyrosine kinase

Question 8

What is Philadelphia (ph) chromosomes

Answer 8

· Ph chromosomes is a cytogenetic defect that is seen as a shorten version of human chromosomes of 22 in CML

· Presented in 90-100% CML
And 25% of ALL

Question 9

What is c-myc

Answer 9

· Is the prototype for oncogene activation by chromosomal translocation

· Regulated expression of c-myc in normal cells
c-myc is deregulated in human cancer

Question 10

What is a Burkitt’s lymphoma

Answer 10

c-myc breakpoint differs in sporadic and endemic Burkitt’s

Varies the types as patients who have EBV are 97% likely to have endemic Burkitt’s
20-30% of are sporadic cases

Question 11

What is a Burkitt’s lymphoma

Answer 11

c-myc breakpoint differs in sporadic and endemic Burkitt’s

Varies the types as patients who have EBV are 97% likely to have endemic Burkitt’s
20-30% of are sporadic cases

Question 12

Describe the different types of Burkitt’s lymphoma

Answer 12

(8: 14- IgH
8: 22-IGbeta
2: 8- IGk

Question 13

What defect does Ph have

Answer 13

T(9:22)(q32:q11)

C-abl in chromosome s9 (tyrosine kinase)

Bcr on chromosomes 22 (protein)

Question 14

What lymphoma is it found

Answer 14

90-100% of adult CML

20-30% of adults ALL

5% in childhood ALL

Question 15

What is shown in microscopy if you see chromosomes

Answer 15

Bacteria and chromosomes

Not viruses

Question 16

What is BCR-ABL protein

Answer 16

• Wt. abl gene shuttles between nucleus and cytoplasm
• Activates tyrosine kinase
• Phosphorylates many substrates
• Can transform in hemopoietic cells
Protects hematopoietic cells from apoptosis

Question 17

How is the function of ABL-BCR effect abl-bcr fusion to activate Tyrosine kinase

Answer 17

• In normal BCR is presented in the cytoplasm
  
  • And in the nucleus there is low levels of ABL proteins resulting in low kinase activity
  • In leukaemia patients, BCR and ABL are joined in the cytoplasm for kinase activity

Question 18

What does it means by ph + in ALL

Answer 18

Worst outcome for children’s

DFS(disease free survival) is 49% at 5yold if wbc at diagnose sis <50,000

DFS 20% at 5yold is wbc is >100,000

Question 19

What are the treatments of ph + ALL

Answer 19

• Bone marrow transplantation

Question 20

What is STI 571

Answer 20

• BCR-ABL; inhibitor
  
  • Daily oral therapy
  • Given to patients in chronic phase
  • Patents achieves complete responses in terms of haematology and cytogenetic
  Less serve side effects

Question 21

What is follicular lymphomas

Answer 21

• Mutation is t(14,18) (q32,q31)
	• Types of non Hodgkin lymphoma disease
	• Bcl-1 is on chromosomes 18
	• Which is a regulator of apoptosis 
Ig heavy chain on chromosomes 14

Question 22

Although mantle cell lymphoma, CLL/SLL follicular lymphoma, and marginal zone lymphoma may all be comprised of small B cells, mantle cell lymphoma has a more aggressive course. This clinical behavior is thought to be due to which of the following

Answer 22

overexpression of cyclin D1.

Question 23

•
A pharmaceutical company approaches you for advice. They have developed a new drug that decreases bcl-2 protein synthesis and that, in combination with standard chemotherapy, shows promising results in follicular lymphoma. They would like to use it in other malignancies. Based on the mechanism of action of the drug and the molecular basis and pathophysiology of the diseases, which of the following would be the next best candidate malignancy to test to drug on?

Answer 23

CLL/small lymphocytic lymphoma (SLL), del 13q12 subset

Question 24

What is T cell lymphomas

Answer 24

• Translocation often involves in T cell cell receptor genes
a rare type of cancer that begins in white blood cells called T cells (T lymphocytes)

Alpha and s chain on 14q11-14

Beta chain on 14q32-36

Gamma chain on 7p15

There are many orter oncogenes such as Lyll and transcription factors families