الفهرس 
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Abstract
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder
originating from an abnormal hematopoietic stem cell and resulting in clonal
proliferation of malignant myeloid progenitor cells. More than 95% of patients have a
distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph+). The Ph
chromosome is derived from the translocation of DNA, between chromosomes 22 and
9. The translocation carries a specific fusion gene known as BCR-ABL, which encodes
constitutively activated tyrosine kinases, whose activities interfere with cellular
proliferation, cell death and interaction with the stromal microenvironment.
Imatinib is a first generation TKI which is used widely as a treatment for CML.
However, resistance to Imatinib was developed by many mechanisms. One of this
mechanism of resistance is overexpression of efflux pump P-glycoprotein. In the
current study, we focused on the ABCB1 (MDR1) genotype. We analyzed the 2 most
relevant single nucleotide polymorphisms of MDR1 the G2677T and C3435T
polymorphisms in 77 Egyptian patients having CML in the chronic phase and treated
with imatinib.
All patients were subjected to the following at diagnosis: complete history
taking and clinical examination with special stress on the size of the spleen below the
costal margin to calculate the Sokal score, complete blood picture, (RQ-PCR) for bcr-abl transcript level and PCR to detect the genotypes of G2677T and C3435T
polymorphisms. All patients were followed up for 1 year. The following investigations
were done at follow up: complete blood picture every 2 weeks until chr achieved then
every 3 months, molecular analysis (RQ-PCR) for bcr-abl transcript level every 3
months, PCR to detect the genotypes of G2677T and C3435T polymorphisms after 12
months.
In the present study, BCR-ABL transcripts level < 10% at 3 months was present
in 34 patients, while those with BCR-ABL > 10% were 43 patients. After 12 months
follow up, 35 patients have achieved MMR. Among those patients, 34 (97.7%) of them
had BCR-ABL < 10 at 3 months of therapy. Concerning C3435T , the frequency of the
CC, CT and TT genotypes in the responding group was (23.5%, 52.9% and 23.5%
respectively) while in the non-responding group was (39.8%, 48.8% and 11.6%
respectively). In the G2677T, the frequency of GG, GT and TT genotypes in the
responding group was (17.6%, 58.8% and 23.5% respectively) while in the non-responding group was (37.2% ,58.1% and 4.7% respectively).
The current study findings indicate that 2677G allele carriers might be at risk
for imatinib resistance while the C3435T genotypes might not be a risk factor in the
development of imatinib resistance.