Chronic Myeloid Leukemia

(CML)

GULZAR A. BHAT
 What is C
ML ?
Chronic
myeloid l
cancer of eukemia
the blood is a
which to system in
o many w
(WBCs) a hite bloo
re made i d cells
n the bon
marrow. e
Robein an
d Ulrich;200
3
 MOLECULAR BASIS
• Leukemic white blood cells in CML
contain a Philadelphia (Ph)
chromosome.
• The Ph chromosome is the result of a
translocation between the long arms of
chromosomes 9 and 22.
This exchange brings together two
genes:
The BCR gene on chromosome 22 and
the proto-oncogene ABL on
chromosome 9.
Nowell PC (2007).
 N F UC TIO N
N PROTI E
BCR-ABL FUSIO

Nowell PC (2007).
 CML

Signs Bruis Fatig

and ing ue

Symptoms Swelling
of the
Weigh
spleen t Loss

Because many people with early CML have no

symptoms, about half of CML cases are detected
when a person visits a doctor for a routine
checkup or blood test.
 CML DIAGNOSIS
Blood Test
 Blood cell countsBlood Test
 Blood cell examination. A person with CML has a small
number of developing cells called "blast cells" in his or her
blood. Blast cells are not found in the blood of healthy
individuals.
Bone Marrow Test
 CML is diagnosed by detecting the Philadelphia
chromosome detected by FISH or PCR for bcr-abl fusion
gene.
 of 3 to 6 months
• In this phase, there are mostly immature WBCs in the Average duration
blood and bone marrow . Symptoms such as anemia and Blast
recurring infections are typical.
6 to 9 months
• There are some immature leukemia WBCs in the blood average duration of
and bone marrow (between 5 percent and 30 percent). Accelerated
Patients may have fever, poor appetite and weight loss.
5 to 6 years
• There are mostly mature leukemia WBCs in the blood average duration of
and bone marrow and there may be no symptoms of Chronic
leukemia.
Phases of CML
TR
EA Chemotherapy
TM
EN • Bone marrow transplantation
TS
• Removal of the spleen
• The newest treatment is Gleevec®, a
therapy that is believed to interfere with the
action of the abnormalities in CML white
blood cells.
• GLEEVEC
• IMATINIB
• STI-571

Vigneri P et al., 2001

 WHO GETS CML?
CML accounts for approximately 15% of all
leukemia's , with 4,000 to 5,000 new cases
diagnosed in the United States annually.
The incidence of CML is 1.6 to 2.0 cases per
100,000 persons per year, and the incidence is
similar in all countries worldwide.
With the average age of people with CML
around 66 years, CML mostly affects adults.
 2 percent of CML patients are children.
 NS I N C M L
LTE RATI O
I C A
GENET
CML
Abnormalities
Abnormalities
of
of P53,RB1,IRF4,
P53,RB1,IRF4,
cMYC,RAS,
cMYC,RAS,
p16
p16INK4A
INK4A

Translocati Monosomies
Monosomies
Translocati of
ons of
ons e.g.,
e.g., chromosome
chromosome
T(3;21)
T(3;21) etc.
etc. 7,17,Y
7,17,Y

Trisomies
Trisomies ofof
chromosom
chromosom
es
es 8,17,21
8,17,21
Jose –Toma et al., 2007
 I VE S
JEC T
OB
•To determine the mutations of irf-4 gene in
chronic myeloid patients (CML).

Why mutation…
. Ifwe know the nature and position of
mutation we will be able to benefit in the
near future from different therapies that
target specific mutations.
 IRF-4 G EN E
•IRF-4/MUM1/LSIRF
• Location ( 6p25.3)
• Gene of 19.4 Kb with 9 exons and 8 introns
 PL A N O F WO RK
Collection of blood samples

• Extraction of DNA

• Genotyping
Polymerase
Chain
Reaction

Aga
ros
e
Gel
Ele
ctro
pho
resi
s

• Statistical Analysis
Thank You
?