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Title of Thesis

Molecular Genetic Studies of Leukemia in Pakistan

Author(s)

Zafar Iqbal

Institute/University/Department Details
Department of Zoology / University of the Punjab, Lahore
Session
2008
Subject
Zoology
Number of Pages
161
Keywords (Extracted from title, table of contents and abstract of thesis)
Molecular, Genetic, Studies, Leukemia, patients, therapies, Pakistan, fusion, oncogenes, genetictesting

Abstract
Leukaemia is cancer of blood resulting due to abnormal haematopoiesis. Major subtypes of leukaemia are ALL, AML, APL, CLL and CML Genetic abnormalities, driven by environment, are major cause of Leukaemia which give rise to fusion oncogenes. These fusion genes are strongly correlated with and highly differ in degree of disease severity, prognosis and response to anti-leukaemia therapies. Thus, studies on frequencies of fusion oncogenes have a great implication in management of leukaemia in any population.
Frequencies of different fusion genes causing leukaemia in Pakistan were studied using RT-PCR and compared with Western populations. Significant differences were found between both population with respect to frequencies of various fusion oncogenes namely SIL-TAL1, TEL-AML1 (adult ALL), BCR-ABL, E2A-PBX1, TEL-AML1, MLL-AF4 (paediatric ALL) and BCR-ABL splice variants (CML) while no significant differences were observed with respect to frequencies of CBFB-MYH11, AML1-ETO (AML) and PML-PARa (APL) (p=0.01). These results explain the molecular genetic basis of already-reported poor prognosis and survival of paediatric ALL and AML patients in Pakistan. BCR-ABL gene mutations in CML were detected by ASO-PCR. Frequency of Imatinib-resistant CML patients with BCR-ABL gene mutations prior to Imatinib therapy was significantly different from patients without pre-existing mutations (p=0.01). So, molecular genetic of the Pakistani patients also affects response to targeted therapies like Imatinib in CML.
On the basis of these studies, it is inferred that Pakistan leukaemia patients have unique genetic characteristics significantly different from West. Routine molecular genetictesting for leukaemia patients, specifically for BCR-ABL gene mutations, can be very helpful in differential diagnosis, prognosis, treatment and drug resistance management of leukaemia.

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 CONTENTS

 

vi
141 KB
2

1

INTRODUCTION 1
396 KB
3 2 LITERATURE REVIEW 7
1,840 KB
4 3 MATERIAL AND METHODS 31
1,075 KB
5 4 RESULTS 48
1,113 KB
6 5 DISCUSSION 69
1,252 KB
7 6 REFERENCES 86
1,872 KB