Abstract B23: Detection of susceptibility to childhood Acute Lymphoblastic Leukemia (ALL)

Abstract

Abstract Currently, there are no known methods to predict of susceptibility to, and means for prevent Acute Lymphoblastic Leukemia (ALL). We have evaluated and patented a group of proteins dubbed Protein X from a certain strain of Aspergillus Flavus (AF) and developed methods for screening and identifying totally asymptomatic patients in remission of ALL, including long term survivors of this disease, distinguishing them from normal controls. Subject to institutional approved consents/assents, 15-20 ml of blood was obtained from 40 cases of ALL in children and young adults, including long term survivors of ALL. Controls were normal individuals, sickle cell patients undergoing partial exchange transfusion and patients with solid tumors. Mononuclear leukocytes (MNL) of ALL patients in remission and controls were separated using Ficoll Paque Plus (GE Healthcare). Epstein Barr virus (EBV) was obtained commercially. Positive and negative controls for Protein X were aflatoxin and Mycocladus Corymbifera (MC). Avian leukosis virus (ALV) was used as control for EBV. MNL were co-incubated with Protein X ± EBV ± irradiation, for periods of 1-72 hours. Controls were treated identically with appropriate substitutions. Test and control MNLs were examined for genetic markers, NF-κB and cell surface markers (CSM) including CD10/CD19, CD34/CD19, and CD34/CD117. Changes were expressed as percentage of control. Using ELISA, plasmas were tested for antibodies against Protein X ± EBV time experiments reveled 72 hours was optimum for achieving results. Upon 72 hours exposure of MNL from ALL to Protein X ± EBV, cells from ALL patents in remission developed cell surface phenotypes typical of ALL. This was not seen in controls. Addition of EBV ± radiation to Protein X, enhanced these effects in MNL of ALL and not controls. Changes were statistically significant and clearly separated ALL from controls. Evaluation of NF-κB revealed enhancement in ALL and not controls. Aflatoxin indiscriminately induced cell surface marker changes in both, normal and ALL, while ALV and supernatant of MC had no effect. ELISA, using Protein X ± EBV, distinguished ALL from controls. Gene array and biomarkers confirmed transformation to leukemic cell markers upon exposure to Protein X in cells from ALL patients but not controls. These studies reveal, in vitro, upon exposure to Protein X, unlike normal controls, MNL from ALL patients in remission develop cell surface phenotypes and genetic markers typical of ALL. These techniques have potential for screening for ALL and may have implications for etiology of ALL and its prevention. Citation Format: Cameron K. Tebbi. Detection of susceptibility to childhood Acute Lymphoblastic Leukemia (ALL). [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B23.