Up-Regulation of GABAergic Signal Events in Bone Marrow Lymphocytes in Childhood Acute Lymphoblastic Leukemia.

Gamma-aminobutyric acid (GABA) is involved in the proliferation, differentiation, and migration of several cell types including cancer cells. Whether GABA may be involved with acute lymphoblastic leukemia (ALL) is unclear. Therefore, the goal of this report was to examine if GABAergic signaling expression is altered in bone marrow lymphocytes of ALL children. RT-PCR and western blot analysis were used to examine the expression of the GABA synthetizing enzyme glutamic acid decarboxylase (GAD) isoforms (GAD65 and GAD67), and type-A GABA receptor (GABA(A)R) subunits [alpha(1-6), beta(1-3), gamma(1-3), delta, epsilon, theta, pi, and rho(1-3)] in bone marrow lymphocytes of 19 ALL children before chemotherapy. The data obtained were compared with those in 13 age-matched non-ALL children. Immunofluorescent staining was used to examine the cellular localization of GAD. We found that GAD and GABA(A)R subunits were expressed in bone marrow lymphocytes of ALL children. Moreover, RT-PCR and western blot showed that GAD and several GABA(A)R subunits were significantly increased in ALL children as compared with the data of non-ALL children. Our present study reveals up-regulation of GABAergic signaling events in bone marrow lymphocytes in ALL children. However, the role of this signaling system in lymphocyte proliferation and invasion as related to the progression of ALL requires further investigation.