Investigating the Correlation Between TGF-β Gene Expression and Disease-Related Prognostic Factors in Bone Marrow Aspiration of Adults With Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites and the second most common acute leukemia in adults. While dose-intensification strategies have led to a significant improvement in outcomes for pediatric patients, the prognosis for the elderly remains very poor. Aberrant or excessive expression of cytokines may be related to the pathogenesis of acute leukemia. TGF-β is a cytokine that plays a role in regulating various cellular processes such as growth, proliferation, and apoptosis. We evaluated the expression of TGF-β mRNA in adults with ALL compared to the control and its relationship with disease-related prognostic factors. Bone marrow specimens were obtained from 90 newly-diagnosed adults with ALL and 33 healthy adults. After immunophenotyping by flow cytometry, RNA was extracted, and RQ-PCR was done. Our result showed that from all patients, 63 (70%) were identified as B-ALL and 27(30%) as T-ALL. TGF-β transcript levels in both T-ALL and B-ALL patients showed a significant decrease compared to the control group (P < 0.001). However, the expression of the TGF-β transcripts was not different between the different immunophenotypic subtypes (P=0.54). The gene expression level of TGF-β was not correlated with age (P=0.47), gender (P=0.29), ALL subtypes (P=0.54), the percentage of bone marrow blasts (P=0.92) and peripheral blood leukocyte count (P=0.38) of ALL patients. In conclusion, since TGF-β has a tumor suppressor role, it seems that leukemic cells may use TGF-β down-regulation to be more freely proliferated and evolve the clone.

Keywords

• Acute lymphoblastic leukemia
• TGF-β
• Immunophenotyping
• RQ-PCR