Similarities between the mechanisms of AIDSassociated NonHodgkin lymphoma and endemic Burkitt lympho

1
Similarities between the mechanisms of
AIDS-associated Non-Hodgkin lymphoma and endemic
Burkitt lymphoma

• Presented by
• Alexis Morante
• Bio 475
• Haluska, F.G., G. Russo, J. Kant, M. Andreef, and
  C.M. Croce.1989. Molecular resemblance of an
  AIDS-associated lymphoma and endemic burkitt
  lymphomas Implications for their pathogenesis.
  Proc. National Academy of Science 868907-8911

2
Non-Hodgkin Lymphoma- outline

• AIDS-related lymphoma
• Burkitt lymphoma
• Symptoms
• Diagnosis
• Staging
• Risk Factors
• Treatment
• Molecular resemblance proven by Haluska et al.

3
What is Non-Hodgkin Lymphoma (NHL)?

• Cancer that develops in the lymphatic system
• Affects white blood cells
• Cells in the lymphatic system become abnormal
• Cells divide and grow without control
• May occur anywhere in the body

4
Stem Cell - Overview

• Bone marrow produces stem cells that develop into
  mature blood cells.
• There are three types of mature blood cells
• -Red blood cells -White
  blood cells
• -Platelets

5
Lymphatic System

• Components
• -Lymph
• -Lymph vessels
• -Lymph nodes
• -Spleen
• -Thymus
• -Tonsils
• -Bone marrow

6
Common symptoms of NHL

• Weight loss
• Fever for no known reason
• Night sweats
• Painless, swollen lymph nodes

• Fullness under ribs
• Constant fatigue
• Unexplained weight loss
• Itchy skin

7
Diagnosis of Non-Hodgkin Lymphoma

• Physical Exam
• Complete blood count
• Lymph node biopsy
• Bone marrow aspiration
• HIV test
• Epstein-Barr virus
• Chest x-ray
• Lymphanogiogram
• MRI and CT scan

8
Types of Non-Hodgkin Lymphoma (NHL)

• Cell appearance under a microscope
• Burkitt lymphoma
• Aggressive and indolent lymphoma
• AIDS-associated lymphoma

9
Classifying NHLs

• Extent of disease
• The number and location of affected lymph nodes
• Location of affected lymph nodes, if they are
  above, below, or on both sides of the diaphragm
  (the thin muscle under the lungs and heart that
  separates the chest from the abdomen)
• Determine if disease has spread to the bone
  marrow, spleen, or to organs outside the
  lymphatic system, such as the liver.

10
Stages of NHLs

• Stage I
• -Stage I
• -Stage IE
• Stage II
• -Stage II
• -Stage IIE

• Stage III
• -Stage III
• -Stage IIIE
• -Stage IIIS
• -Stage IIISE
• Stage IV

11
What Treatments are Available?

• Primary treatment is chemotherapy.
• Treatment for children is complex and involves
  multiple drugs.
• Depends on stage and if it is indolent or
  aggressive.

12
Therapy for Standard Treatment

• Chemotherapy
• -Systematic chemotherapy
• -Intrathecal chemotherapy
• -Combination chemotherapy
• Radiation Therapy
• -External radiation
• -Internal radiation

13
Risk Factors

• Older, male or white
• Inherited immune disorder
• Autoimmune disease

• HIV/AIDS
• Epstein-Barr virus
• Past treatment of lymphoma or with radiation

14
Molecular resemblance of an AIDS-associated
lymphoma and endemic Burkitt lymphomas
15
Important Terminology

• t(814) translocation
• MYC oncogene
• Epstein-Barr Virus

• Immunosuppression
• Probe pHj
• B-cell

16
Immunoglobulin

• A general term for the kind of globular proteins
  that constitute antibodies.
• Tetrameric protein composed of two identical
  light chains and two identical heavy chains.
• pHj probe detects immunoglobulin heavy chain
  joining (JH) segments on chromosome 14.

17
Similarities between AIDS-associated lymphoma and
Burkitt lymphoma

• Carry Epstein-Barr Virus genome
• Immunosuppression
• t(814) translocation
• Expansion of B-cell population

18
Rational

• Molecular analysis to prove that there is a
  relationship between the AIDS-associated
  Non-Hodgkin Lymphoma and Burkitt Lymphoma, such
  as the t(814) translocation.

19
Materials and Methods

• DNA extraction and blotting procedures
• Molecular probes
• -pHj probe
• -MYC probe
• Southern Blot

20

• How can it be demonstrated that rearrangement of
  the patients JH region takes place?

21
Molecular Analysis of t(814) translocation

• DNA extraction from tissue of lymph node
• Digested with enzymes for southern analysis
• Rearrangement of immunoglobulin JH segment
  observed
• MYC was not seen to have any rearrangement
• Depending on break point will affect the size in
  the DNA electrophoresis
• MYC had no rearrangement

22
Southern Blots of Control and Patient
Placental and patient DNA (BAMH1 Probe)
Placental and patient DNA (Hind III)/MYC
Placental and patient DNA (Hind III/pHj)
23
Is there any way of identifying the t(814)
translocation break point?
24
Identification of the t(814) break point

• Hypothesized that t(814) breakpoint was far
  from MYC and within the JH region.
• Chromosome 14 pHj probe was used for screening.
• 1.9 kilobase (kb) Hind III fragment
• Designated H1.9, originated from chromosome 8.

25
Restriction Map

• Fig 2?????????????????NEED TO SCAN FIGURE

26
Does H1.9 hybridize to chromosome 8 and
chromosome 14? Or does it hybridize to only one
of them?
27
Southern blot(Hind III human DNAs probed with
pH1.9)
Chromosome 8 w/ deletion of MYC
Chromosome 8 but not 14
Chromosome 14 but not 8
28

• Fig4??????????

29
Results
30
Conclusion
31
Reference