Association between Antiapoptotic Marker (BcL2) and Philadelphia chromosome in Newly Diagnosed Childhood Acute Lumphoblastic Leukemia

Gihan El-Hussiney Gawish *; Ahmed A. Settin**; Abdelfattah M. Attallah***

Biochemistry Dep., Faculty of Science, King Saud University*; P

ediatrics and Genetics Dep., Faculty of Medicine, Mansoura University**; 

Biotechnology Research Center, New Damietta***

The purpose of this investigation was to evaluate the many biomarkers related to Philadelphia chromosome using flowcytometry and FISH techniques in newly diagnosed childhood acute lumphoblastic leukemia to help in diagnosis and prognosis.

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer.  ALL accounts for about 75% of childhood leukemia and 25% of all pediatric cancer. Many clinical, biological, genetic, and molecular features have been identified as having prognostic significance in the outcome of patients with ALL.

The presence of the t(9;22)(q34;q11) translocation, commonly known as Philadelphia chromosome (Ph), is considered as one of the molecular markers. This translocation causes a rearrangement between the protooncogene c-ABL and a gene called the breakpoint cluster region (BCR). Whereas the breaks in c-ABL occur mainly in the same region (between the axons a1 and a2) on chromosome 9, two different ones affect the breakpoint cluster region on chromosome 22. The BCR/ABL fusion genes was considered as a high risk prognostic factors in children with (ALL).  Ph+ cases require early identification to permit treatment with intensive induction regimens and experimental approaches such as bone marrow transplantation. The Philadelphia translocation can be detected by Fluorescence in situ hybridization (FISH).

Complex pathways exist for the regulation of the cell cycle and apoptosis. Abnormalities in the expression or function of key proteins in either of these regulatory pathways could confer proliferative advantages to leukemic cells and, thereby, contribute to leukemogenesis. Most antileukemic chemotherapy functions via induction of apoptosis; consequently, sensitivity or resistance of leukemic blasts to chemotherapy may correlate with the apoptotic potential of a cell. The oncogenic activity of the Bcl2 gene is carried out via suppression of lymphocytic apoptosis or programmed cell death. Bcl2 protein promotes cell survival by preventing apoptosis. BcL2 exerts an antiapoptotic effect on cells and decreases chemosensitivity. The measurement of BcL-2 by flowcytometric techniques has received by using fluorescence antibodies.

     We have concluded that among children with acute lymphoblastic leukemia (ALL) 18% patients were found to have Philadelphia chromosome-positive (Ph⁺) ALL, patients who were found to be positive for BCR/ABL or t(9;22). These patients were analyzed for presenting features and treatment outcome to identify specific prognostic factors.  We have observed that all patients with Ph⁺ had allogeneic bone marrow transplantation (allo-BMT). Also, we found that the median age of Ph⁺ patients was 7.5 years. The median white blood cell count (WBC) was 75×10⁹/L. We observed that Ph+ patients have high levels of hemoglobin and BCL2 expression. Conclusion: we can recommended that each newly diagnosed  childhood ALL with highly Bcl2  level, leukocyte count, hemoglobin level and older age should be analyzed by FISH technique for detection of Philadelphia to help in successful treatment. Cytogenetic and molecular biology studies provide more information in prognostic prediction of ALL.