BCR-ABL TRANSLOCATION

AND EXPRESSION

Presenters
Germaine Daley & Anthonesha Henry

OBJECTIVES
At the end of this session you will be able to explain:
BCR-ABL translocation

The association of BCR-ABL translocation with Chronic Myelogenous

Leukaemia

DEFINING IMPORTANT
TERMS
Cancer (group of disease involving unregulated or poorly regulated cell

division)

Proto oncogene(genes that code proteins that help regulate cell division)
Oncogene codes for a protein that interferes with the regulation of cell

division

Chronic Myelogenous Leukaemia (A type of cancer where there is an

increase in white blood cell production)

ABL (Abelson murine leukemia viral oncogene homolog1gene)

cAbl in Humans, vAbl viruses

BCR (Breakpoint cluster region gene)

SOME MECHANISMS FOR

CANCER DEVELOPMENT
Spontaneous mutation (BCR-ABL translocation and expression) Philadelphia

chromosome

Hereditary (Colon cancer)

Occupational ( working with fibre glass Edna Manley or asbestos)
Chemicals consumption of nuts (aflatoxins)
Viral infections (HPV implicated in cervical cancer)

BCR-ABL TRANSLOCATION

Piece of chromosome 9 swapping places with a piece of chromosome 22

BCR-ABL TRANSLOCATION &

CHRONIC MYELOGENOUS
LEUKAEMIA

BCR-ABL TRANSLOCATION
AND EXPRESSION

SYMPTOMS
Lethargy

Fever

Weight loss

Pain or fullness below the rib

Bleeding

SIGNIFICANCE AND
INCIDENCE
5000 diagnosed in US/yr
Problem reluctance to invest in initial drug development

250000 Brest cancer in US/yr

TREATMENT OPTIONS RX
Bone marrow transplant
Cost 1 Mil US/yr + 1yr recovery (BMT)
Long term, problem= immunosuppressive therapy

BCR-ABL tyrosine protein kinase inhibitor imatinib mesylate (Gleevec,

Novartis Pharmaceuticals,Basel, Switzerland) (originally known as STI571 and

CGP57148B) targets the enzymatic activity of the Bcr-Abl protein
Cost 100k US/yr
Short term, works once treatment continues

REFERENCE
Quintas-Cardama, A, Kantarjian, H, Jones, D et al, Dasatinib (BMS-354825)

is active in Philadelphia chromosome-positive chronic myelogenous

leukemia after imatinib and nilotinob (AMN107)therapy failure. Blood.
2007;109:497499.

QUESTIONS