The prognostic role of C-KIT, TET1 and TET2 gene expression in Acute Myeloid Leukemia.

AIM: was to assess the role of C-KIT, TET1 and TET2 expression in the diagnosis and prognosis of acute myeloblastic leukemia (AML). METHODS: The expression levels of C-KIT, TET1 and TET2 were assessed in the bone marrow (BM) aspirate of 152 AML patients compared to 20 healthy control using quantitative real-time polymerase chain reaction (qRT-PCR). Data were correlated with the clinico-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall survival (OS) rates. RESULTS: C-KIT, TET1 and TET2 were significantly upregulated in AML patients [0.25 (0-11.6), 0.0113 (0-3.301), and 0.07 (0-4); respectively], compared to the control group [0.013 (0.005-0.250), P < 0.001, 0.001 (0-0.006), P < 0.001, and 0.02 (0.008-0.055), P = 0.019; respectively]. The sensitivity, specificity, and area under curve of of C-KIT were (48.7%, 100%, 0.855; respectively, P = 0.001), and that of TET1 were (63.4%, 100%, 0.897; respectively, P = 0.001), while that of TET2 were (56.8%, 100%, 0.766; respectively, P = 0.019). When combining the three markers, the sensitivity was 77.5%, however it reached the highest sensitivity (78.6%) and specificity (100%) when combining both c-KIT + TET1 together for the diagnosis of AML. C-KIT overexpression associated with shorter DFS (P = 0.05) and increased incidence of relapse (P = 0.019). Lymph nodes involvement [HR = 2.200, P = 0.005] is an independent risk factor for shorter OS rate of AML patients. Increased BM blast % [HR = 7.768, P = 0.002], and FLT3-ITD mutation [HR = 2.989, P = 0.032] are independent risk factors for shorter DSF rate of the patients. CONCLUSION: C-KIT, TET1, and TET2 could be used as possible useful biomarkers for the diagnosis of AML.

SMYD2 Expression: Its Relationship to Cytogenetic and Prognosis in a Newly Diagnosed Childhood B-Acute Lymphoblastic Leukemia.

BACKGROUND: The SMYD2 gene adjusts lysine residues on histones and non-histone proteins such as transcription factors, signaling kinases, and cell cycle regulators affecting the cell fate and other genes' expression. As it acts as an oncogene, SMYD2's expression levels may affect tumor progression. In this prospective study, our main aim was to determine the association of SMYD2 gene expression with the prognostic parameters of childhood B-acute lymphoblastic leukemia (B-ALL) and evaluate its influence on disease prognosis. METHODS: SMYD2 gene expression was measured in the peripheral blood (PB) samples of 116 newly diagnosed B-ALL patients and 23 controls using real-time polymerase chain reaction (RT-PCR). RESULTS: SMYD2 expression was significantly higher in the childhood B-ALL patients compared with the control group, p-value < 0.001. The patients with unfavorable rather than favorable structural chromosomal abnormalities had significantly higher SMYD2 mRNA levels, p < 0.001. SMYD2 expression levels were positively correlated with total leucocytes count (r = 0.206, p-value = 0.027) and peripheral blood blasts (r = 0.225, p-value = 0.015). There was a statistical difference between the B-ALL cases with high versus low SMYD2 levels regarding translocation (t12; 21), p-value = 0.015. Cox regression analysis identified the increased levels of SMYD2 as an independent prognostic factor affecting both OS and DFS. CONCLUSIONS: The SMYD2 gene plays a vital oncogenic role in childhood B-ALL. The association of high SMYD2 levels with unfavorable cytogenetics in childhood B-ALL may be helpful in understanding the relationship between structural chromosomal abnormalities and epigenetic dysregulation. High SMYD2 levels may be useful in the prediction of prognosis in childhood B-ALL.

Prognostic Impact of PPP2R5C Gene Expression in Adult Acute Myeloid Leukemia Patients with Normal Cytogenetics.

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.