BACKGROUND: Leukemia is defined as a neoplastic proliferation of hematopoietic tissue of white blood cell precursors in bone marrow CML accounts for 20% of all leukemias in adult patients. One of the characteristic findings in CML subjects is the presence of the Philadelphia (Ph) chromosome and Bcr-Abl oncogene. Philadelphia (Ph) is the shortened chromosome 22, formed by reciprocal translocation between the long arms of chromosomes 9 and 22, t (9; 22). OBJECTIVES OF STUDY: — To determine the frequency of Philadelphia chromosome in CML. — To evaluate the standard and variant translocation in CML. — To determine frequency of other chromosomal abnormalities in Philadelphia +ve CML. — To detect bcr-abl gene rearrangement and to determine the frequency of the b2a2 and b3a2 transcripts in Philadelphia + CML by PCR. SUBJECTS AND METHODS: The study was conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro and Isra University Hospital, Hyderabad during May-to-September 2014. Bone marrow and peripheral blood samples from a total of 145 diagnosed cases of CML were collected. Cytogenetic analyses were performed using karyotyping as per the international system for human cytogenetic nomenclature guidelines. All karyotpic images were analyzed using the Cytovision software. In order to identify BCR-ABL transcripts, RT-PCR was performed. Statistical analysis of the data was done using SPSS-version-21.0. Results: Of the 145 samples, a total of 133 (91.7%) were positive for the Ph (Ph+) while 12 (8.2%) were negative for the Ph (Ph-). Of the 133 Ph+ samples, standard chromosome was noted in 121 (90.9%), simple variant in 9 (6.7%) and complex variants in 3 (2.2%) of the samples. All the Ph+ samples (n=133) showed BCR-ABL positivity. Of the 12 Ph- samples, a total of 7 (58.3%) were BCR-ABL-positive and 5 (41.6%) were BCR-ABL-negative. Various types of molecular abnormalities were noted in in responders and in non responders as shown in table below. Out of 11 patients, who responded on Glivec, 8 patients showed b3a2 transcripts abnormality while 3 cases had b2a3 abnormality. Both non-responders showed b2a2 + e 19a2 transcripts. CONCLUSION: Philadelphia frequency of 90.9%. Out of 133 Ph +ve all were bcr-abl +ve while out of 12 Ph-ve 7 were bcr-abl +ve while 5 were –ve. Cytogenetic and molecular analysis has become mandatory in order to make a correct diagnosis and predict/monitor response to newer molecular targeted treatment modalities. KEY WORDS: Philadelphia chromosome, BCR-ABL, Chronic Myeloid Leukemia, cytogenetic analyses, Sindhi population.