Date of Publication

4-2010

Document Type

Master's Thesis

Degree Name

Master of Science in Biology

Subject Categories

Immunology and Infectious Disease

College

College of Science

Department/Unit

Biology

Thesis Adviser

Ma. Luisa D. Enriquez

Defense Panel Chair

Esperanza C. Cabrera

Defense Panel Member

Michael B. Ples
Ma. Luisa G. Daroy

Abstract/Summary

Chronic myelogenous leukemia (CML) is the first cancer known to be associated with reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11). Monitoring of the disease is important to detect early evidence of residual malignant cells (MRD). The aim of the study is to identify cytogenetic and molecular changes in CML patients undergoing chemotherapy. Ten (10) CML patients initially diagnosed by a hematologist and with 2 succeeding follow-ups were included in the study. Bone marrow aspirate (BMA) samples at initial diagnosis were processed using GTG-banding, Nested RT-PCR, DNA sequencing and RQ-PCR. The 2 succeeding follow-ups after treatment with a tyrosine kinase inhibitor (Imatinib), BMA samples were monitored using: GTG-banding, Nested RT-PCR and RQ-PCR. Standardizing in expressing and interpreting of results for RQ-PCR are in progress. All CML patients were Ph postive at diagnosis. Eighty percent (80%) of the samples are of the b3a2 type. Secondary chromosome abnormalities both structural and numerical have been observed in some patients while undergoing treatment and these are thought to be brought about by drug treatment. In the first follow-up after initiating chemotherapy, 30% were classified in complete cytogenetic response but at the molecular level, both qualitative and quantitative tests (RT-PCR and RQ-PCR) they are not responding to the treatment because of the persistent presence of the BCR-ABL transcript. In the second follow-up 60% were classified in complete cytogenetic response but still exhibit the molecular markers of the disease. RQ-PCR was able to detect very low number of copies of BCR-ABL gene which makes it an excellent method in detecting MRD. Cytogenetic analysis revealed numerical and structural and even complex chromosome changes in the course of chemotherapy and these include: near-triploidy, hypodiploidy and monosomy of chromosomes and atypical CML translocation. Molecular change in the BCR-ABL gene quantity was also detected and was the basis of classifying patients into different molecular responses (major, partial or no response) even in the absence of Ph chromosome. The cytogenetic findings in this study are strengthened by the molecular data.

Abstract Format

html

Language

English

Format

Electronic

Accession Number

CDTG004697

Shelf Location

Archives, The Learning Commons, 12F Henry Sy Sr. Hall

Physical Description

v, 62 leaves

Keywords

Chronic myeloid leukemia; Chemotherapy

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