Exposure to a mycovirus containing Aspergillus Flavus reproduces acute lymphoblastic leukemia cell surface and genetic markers in cells from patients in remission and not controls.

The etiology of acute lymphoblastic leukemia (ALL) remains unknown. A recent "two-hit" model for the occurrence of precursor B cell acute lymphoblastic leukemia propose that this disease arises through a two-step process, including predisposing genetic mutation and exposure to infections. While several genetic mutations are proposed, no infection category has been suggested. We have isolated a certain Aspergillus Flavus from residence of an ALL patient. This organism contains mycovirus and does not produce aflatoxin. The supernatant of culture of this mycovirus containing Aspergillus Flavus (SAF) was tested on the PBMCs of ALL patients in remission and controls. Cell surface phenotypes and genetic markers were examined. The effects of its combination with Epstein-Barr virus (EBV) was also investigated. For the SAF, positive and negative controls were aflatoxin and culture of Mycocladus corymbifer, respectively. Controls for ALL were sickle cell patients undergoing exchange transfusion. Incubation of the PMBCs from ALL patients in remission, or controls, with SAF resulted in re-development of ALL cell surface phenotypes and genetic markers in ALL patients in remission and not controls. These differentiating effects were not seen with aflatoxin or culture of Mycocladus Corymbifer. Addition of EBV did not alter effects of SAF. Currently, there are no techniques to discriminately reproduce characteristic leukemic genetic markers and cell surface phenotypes in cells from ALL patients in remission and not controls. These studies may provide a test for recognition of ALL patients in remission and new prospects for the investigation of leukemogenesis.

Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolated A. flavus contained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containing A. flavus could differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.