A narrative review of central nervous system involvement in acute leukemias

Abstract

Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although

CD58 as a biomarker for prognosis and immune infiltration in hepatocellular carcinoma

“…Previous studies found that CD58 is a glycoprotein expressed on the surface of B cells, T cells, monocytes, granulocytes and thymic epithelial cells, an important member of the immune superprotein family, and has a role in promoting cell adhesion [19]. We found that the main studies of CD58 focused mainly on hematological tumors [23][24][25]27], skin diseases [35], where CD58 plays a rather important role through different mechanisms. There are also a few other malignant tumors, such as cervical cancer[28],…”

“…Mutations in CD58 and TP53 were found in diffuse large B-cell lymphoma (DLBCL) to be the most promising predictors of poor outcome as prognostic markers [26]. The main cause of patients with leukemia with central nervous system (CNS) invasion is related to the expression of speci c adhesion molecules, such as CD58, by subpopulations of leukemic cells [27].…”

In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia

“…The CNS is an immune-privileged site that can protect leukemic cells from chemotherapy. Overexpression of the neural cell adhesion molecule NCAM/CD56 in the surface of leukemic stem cells increases their ability to infiltrate the CNS [70]. In this regard, deterministic deregulation of selected neuronal signaling pathways may hypothetically enable leukemic cells to 'mingle' within the neuronal tissue microenvironment and rewire with the electrically active neurons [70].…”

“…Overexpression of the neural cell adhesion molecule NCAM/CD56 in the surface of leukemic stem cells increases their ability to infiltrate the CNS [70]. In this regard, deterministic deregulation of selected neuronal signaling pathways may hypothetically enable leukemic cells to 'mingle' within the neuronal tissue microenvironment and rewire with the electrically active neurons [70]. On the other hand, Hanoun et al (2014) demonstrated that adrenergic signals regulate AML and that when leukemic cell injections in mice are followed by sympathetic denervation, the course of disease is accelerated.…”

“…The branches in the dendrogram represent modules, and each leaf, which is a short vertical line, corresponds to a gene. A total of 17 gene co-expression modules were determined, labeled as turquoise (735), blue (512), brown (308), yellow (277), green (258), red (238), black (223), pink (218), magenta (202), purple (186), greenyellow (139), tan (134), salmon (81), cyan (76), midnightblue (70), lightcyan (69), and grey60 (58); the numbers in the parentheses indicate the number of genes per module. The unclustered genes (10) were assigned to the gray module.…”