RESUMO
Protein Phosphatase 2A (PP2A) is a crucial regulator of the cellular signalling pathways, proliferation, cell cycle checkpoints and apoptosis. The PPP2R5C gene encodes PP2A regulatory B56γ subunit. Malignant transformation may occur, if mRNA of PPP2R5C is functionally deregulated, structurally altered, decreased or overexpressed. Therefore, the purpose of the study was to examine PPP2R5C mRNA expression, evaluate its association with the different clinical and haematological parameters and determine its prognostic impact in Egyptian adult acute myeloid leukaemia patients with normal cytogenetics (CN-AML). Peripheral blood samples of 50 de novo CN-AML patients and 20 age- and gender-matched healthy controls were examined for PPP2R5C expression by Quantitative Real Time-Polymerase Chain Reaction. The expression levels of PPP2R5C mRNA were significantly higher in the CN-AML samples than in the control samples (P ≤ 0.001). There was a statistical significant difference between the low and high expression levels of PPP2R5C with regard to age (P = 0.005, r = - 0.447, P = 0.001). The patients with an unfavourable response to induction chemotherapy had significant higher PPP2R5C expression levels than those with a favourable response (P = 0.002). There was a significant influence of high PPP2R5C expression levels on the overall survival and progression free survival (P = 0.03, 0.026), respectively. PPP2R5C overexpression is an adverse prognostic factor which affects leukaemogenesis in the CN-AML, it may predict the disease progression and overall survival during the follow-up of the patients.
RESUMO
BACKGROUND: Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse. OBJECTIVES: We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients. PATIENTS AND METHODS: Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). RESULTS: Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). CONCLUSION: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.