BCH3042 Lecture Notes - Lecture 13: Chronic Myelogenous Leukemia, Receptor Tyrosine Kinase, Chromosomal Translocation

77 views3 pages
Lecture 13 Chronic Myeloid Leukaemia (CML) and BCR/Abl
Single oncogenic mutation causes CML
Chromosomal Rearrangement
Many affect oncogenes or transcription factors
Rearrange the regulatory and coding regions of these genes gene product is
MORE active or expressed at higher levels
Genetics alterations have important prognostic implications
Leukemia translocations activate genes in stem cells with multi-lineage and
self renewal capacity
Translocation generated oncogenes transform committed progenitors
Chronic Myeloid Leukemia
Novel drug therapies developed from understanding the molecular basis of
human cancers
Consistent acquired genetic lesion involving chromosomal translocation
Only detected in leukemic cells (20% of all)
A Fatal disorder (3-5 years)
o Now curable with new therapies
Affects patients in their 30s and 40s
Diagnosis
o Single abnormal HSC
o Proliferation of immature white blood cells in bone marrow and
peripheral circulation blood cell count
o Proliferation in myeloid series but not as primitive cells as seen in
acute leukemia (some differentiation)
More aggressive cancer less differentiated it is
Chronic is more differentiated that acute leukemia
Single genetic lesion in HSC generates a fusion oncogene, BCR-ABL (non
receptor tyrosine kinase)
o Encodes a protein tyrosine kinase that is necessary and sufficient for
cell transformation
o Don’t have ligand binding site outside of cell, inside
o Access to neoplastic clone without need for invasive surgery
CML caused by ABL
Bcr-Abl generated by chromosomal translocation at chromosome 9 and 22
(q34;q11)
3’ sequence from Abl1 proto-oncogene on chromosome 9 with 5’ sequence
from BCR gene on chromosome 22.
SH3 domain on N-terminus: allow for substrate and protein-protein
interactions
SH2 domain: allows for binding to phosphorylated tyrosine residues
Abl resides predominantly in nucleus, and sometimes
cytosol
c-Abl breaks off at chromosome 9 rest translocates
and bind sto Bcr chromosome 22
find more resources at oneclass.com
find more resources at oneclass.com
Unlock document

This preview shows page 1 of the document.
Unlock all 3 pages and 3 million more documents.

Already have an account? Log in

Get access

Grade+20% off
$8 USD/m$10 USD/m
Billed $96 USD annually
Grade+
Homework Help
Study Guides
Textbook Solutions
Class Notes
Textbook Notes
Booster Class
40 Verified Answers
Class+
$8 USD/m
Billed $96 USD annually
Class+
Homework Help
Study Guides
Textbook Solutions
Class Notes
Textbook Notes
Booster Class
30 Verified Answers