NG2 and VLA-4 are involved in the invasion and migration of MLLr B-cell Acute Lymphoblastic Leukemia

B-cell Acute Lymphoblastic Leukemia with MLL gene rearrangements (MLLr B-ALL) is an aggressive subtype of B-ALL (overall survival< 40%), whose patients are usually younger than 1 year and present therapy resistance and high relapse rates. Remarkably, the proteoglycan Neuron-glial antigen 2 (NG2), which is barely expressed in normal hematopoietic cells, is expressed in the leukemic cells of around 90% of MLLr B-ALL patients. However, its role in MLLr B-ALL remains elusive. In recent years, our group has correlated NG2 expression with poor prognosis and central nervous system (CNS) infiltration. Importantly, NG2 has been associated to migration through its interaction with integrins in solid tumors. Our data showed a co-localization of NG2 and integrin α4β1 (ITGA4/ITGB1) by imaging flow cytometry, as well as a higher expression of ITGA4 in NG2-positive sorted blasts, suggesting a cooperation between both proteins. Finally, our in vivo results revealed that mice transplanted intravenously with NG2/ITGA4 double knock-out MLLr B-ALL cell line present long delay in the development of leukemia, suggesting that ITGA4 and NG2 could be cooperating in homing and migration of leukemic cells.

Publication History

Article published online:
12 May 2023