Ppt Cml1 - Copy

8/6/2019 Ppt Cml1 - Copy

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Leukemic white blood cells in CMLcontain a Philadelphia (Ph)

chromosome.

The Ph chromosome is the result of

a translocation between the longarms of chromosomes 9 and 22.

This exchange brings together twogenes:

TheBCR gene on chromosome 22 andthe proto-oncogene ABL on

chromosome 9.

Nowell PC (2007).


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Nowell PC (2007).


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Because many people with early CML have nosymptoms, about half of CML cases are detected

when a person visits a doctor for a routinecheckup or blood test.

CML

Fatigue

WeightLoss

Swellingof thespleen

Bruising


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y Blood cell counts

yBlood cell examination. A person with CML has a smallnumber of developing cells called "blast cells" in his or herblood. Blast cells are not found in the blood of healthy individuals.

y CML is diagnosed by detecting the Philadelphiachromosome detected by FISH or PCR for bcr-abl fusiongene.


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In chronic phase CML,fewer than 10% of cells inblood and bone marrow are blast cells and there maybe no symptoms of leukemia.

Chronic

average duration of5 to 6 years

In accelerated phase of CML ,10% to 20% of the cellsof blood and bone marrow are blast cells. Patientsmay have fever, poor appetite and weight loss.

Accelerated

average duration of

6 to 9 months

In this phase,20% or more cells are blast cells.Symptoms such as anemia and recurring infectionsare typical.

Blast

Average durationof 3 to 6 months


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yChemotherapy

Bone marrow transplantation

Removal of the spleen

The newest treatment is Gleevec, a

therapy that is believed to interfere with theaction of the abnormalities in CML whiteblood cells.


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GLEEVEC IMATINIB STI-571

Vigneri P et al., 2001


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y CML accounts for approximately 15% of allleukemia's , with 4,000 to 5,000 new cases

diagnosed in the United States annually.y The incidence of CML is 1.6 to 2.0 cases per

100,000 persons per year, and the incidence issimilar in all countries worldwide.

yWith the average age of people with CMLaround 66 years, CML mostly affects adults.

y 2 percent of CML patients are children.


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CML

Monosomiesof

chromosome7,17,Y

Trisomies ofchromosomes

8,17,21

Translocations e.g.,

T(3;21) etc.

Abnormalitiesof

P53,RB1,IRF4,

cMYC,RAS,

p16INK4A

Jose Toma et al., 2007


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To determine the mutations ofirf-4 gene in

chronic myeloid patients (CML).

Why mutation

. If we know the nature and position ofmutation we will be able to benefit in thenear future from different therapies that

target specific mutations.


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IRF-4/MUM1/LSIRF Location ( 6p25.3) Gene of 19.4 Kb with 9 exons and 8 introns


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Collection of blood samples

Extraction of DNA

Genotyping

Polymerase Chain Reaction

Agarose Gel Electrophoresis

Statistical Analysis


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Ppt Cml1 - Copy

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