Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL rearrangement.

BACKGROUND: Expression of myeloid or T cell lymphoid in precursor B cell acute lymphoblastic leukemia (pre-B cell ALL), which is referred to as aberrant expression, is quite a common phenomenon. CD66c is a myeloid marker which has aberrant expression in pre-B cell ALL, with strong correlation with non-random genetic changes (BCR/ABL rearrangement). Another leukemia associated marker (CD25) is frequently expressed in pre-B cell ALL. The frequency of CD25-expressing lymphoblasts has been found to be significantly higher in BCR/ABL-positive vs. BCR/ABL-negative patients. METHODS: In a cohort of 103 patients diagnosed with pre-B cell ALL or biphenotypic leukemia and studied for expression of CD66c and CD25 at presentation, we evaluated the frequency of expression of either or both in BCR/ABL positive cases. RESULTS: Surface CD66c was expressed by 70 cases (68%) and CD25 was expressed by 33 cases (32%) while both were expressed together on 29 cases (28%). BCR/ABL was positive in 18/103 patients. All BCR/ABL positive cases were positive for surface CD66c and CD25. CONCLUSION: Positivity for both leukemia-associated antigens CD66c and CD25 in combination can predict the presence of BCR/ABL rearrangement in pre-B cell ALL. While this finding does not replace the detection of BCR/ABL abnormality by cytogenetic or molecular techniques, it does provide an early and handy tool for prediction and management of high-risk cases of pre-B cell ALL, especially in centers with limited laboratory facilities.

Expression of survivin and p16(INK4a)/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells.

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined, and therapeutic approaches based on the genetics of these tumors are currently lacking. In the present study we have used the immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are differentially expressed in primary meningioma cells with 20-, 30- and 36-fold difference between the lowest and the highest levels of each protein, respectively. In addition, we present evidence that the level of the anti-apoptosis survivin protein is high in these benign tumors. Moreover, the annexin V-associated flow cytometry technique was used to show that 60% of meningioma cell cultures underwent apoptosis in response to both gamma-rays and cisplatin, and 50% of these cells exhibited significant sensitivity to hydroxyurea. These agents triggered apoptosis through the mitochondrial pathway, by increasing the Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation and cisplatin was significant in all cells that expressed low levels of p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular biology of meningioma cells and suggest that survivin and proteins of the RB pathway could play a determinant role in the development and the treatment of meningiomas.