Common cytogenetic abnormalities in patients with acute lymphoblastic leukemia at jinnah postgraduate medical center, karachi

Background: Acute Lymphoblastic Leukemia (ALL) is associated with different structural chromosomal abnormalities and altered chromosomal number which represents its genetic heterogeneity. These aberrations could be both structural or numerical as stated above. Structural aberration alters the chromosome structure but do not involve a change in chromosome number. The mechanism involved rearrangement through loss, gain or reallocation of chromosomal segments. Some patients show a loss or a gain of one or few chromosomes, called aneuploidy. The phenomenon arises due to non-disjunction or abnormal distribution of chromosomes during anaphase of meiosis. If the patient has greater than 49 chromosomes, it is regarded as hyperdiploidy. Whereas, if it is between 35-46, it is regarded as hypodiploidy. These chromosomal abnormalities predict patient outcome and prognosis. Therefore, it is essential to evaluate common cytogenetic abnormalities in patients with acute lymphoblastic leukemia for better and more targeted therapeutic regimes.
Objective: To evaluate the frequency of cytogenetic aberrations in adult patients of Acute Lymphoblastic Leukemia at Medical Oncology Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan to have better understanding of the disease and its course in Pakistani population.
Study Design: Cross sectional, observational study.
Place and Duration of Study: This study was conducted at Oncology Department of Jinnah Postgraduate Medical Center, Karachi from April 2016 to September 2017.
Material and Methods: This was a cross-sectional observational study conducted from April 2016 to September 2017 in Oncology ward of Jinnah Postgraduate Medical Center, Karachi after ethical approval. The total of 32 patients with the age range of 14 to 40 years diagnosed with ALL were included in the study by convenient sampling method. Patients who did not give informed consent and those who had started their treatment were excluded from the study. Complete blood picture and cytogenetic analysis was done by using bone marrow sample from Pathology Laboratory of Aga Khan University Hospital, Karachi. The abnormalities found in cytogenetic analysis were classified into numerical and structural abnormalities. The statistical software SPSS version 20.0 was used for data analysis.
Results: In the total of 32 patients included in the study the mean age of the patients was 23.22±8.37 years with male to female ratio of 3:1. The hemoglobin level (Hb) was 8.49±1.82gm%, red blood cell (RBC) count was 2.87±0.77x106 cells/mm3, haematocrit level was 28.29±4.87%, mean corpuscular volume (MCV) was 87.20±13.84cuµ, mean corpuscular hemoglobin concentration (MCHC) was 28.94±3.57%, white blood cells (WBC) count was 54.22±93.56 x103 cells/mm3 and platelet count was 72.96±77.98 x105cells/mm3. The most common cytogenetics observed was diploidy (two sets of chromosomes) in 28(88%). The two numerical abnormalities were hyperdiploidy (47-57chromosomes) in 2(6%) and hypodipolidy (35-45 chromosomes) in 2(6%). The structural abnormalities were present in combination of translocation, deletion and addition. The most common structural abnormality was translocation (t) found in 29(90.5%) patients. Among them the Philadelphia chromosome t(9;22) was the common translocation found in 8(27.5%), followed by t(q34), t(q11.2), t(q23), t(q25) in 7(24%), 5(17.2%), 3(10.3%), and 2(6.8%) patients respectively. All the other translocations were observed in 1(3.4%) cases. The other structural abnormalities were deletion in 5(15.6%) and addition in 5(15.6%) patients.
Conclusion: This study concluded that majority of adult ALL patients in Pakistan had normal chromosome number. Diploidy was found to be most prevalent and among the abnormalities hyperploidy and hypoploidy were noted in. In structural abnormalities, translocation t(9;22) of chromosome was the most frequent aberration.