TY - JOUR
T1 - A narrative review of central nervous system involvement in acute leukemias.
AU - Deak, Dalma
AU - Gorcea-Andronic, Nicolae
AU - Sas, Valentina
AU - Teodorescu, Patric
AU - Constantinescu, Catalin
AU - Iluta, Sabina
AU - Pasca, Sergiu
AU - Hotea, Ionut
AU - Turcas, Cristina
AU - Moisoiu, Vlad
AU - Zimta, Alina-Andreea
AU - Galdean, Simona
AU - Steinheber, Jakob
AU - Rus, Ioana
AU - Rauch, Sebastian
AU - Richlitzki, Cedric
AU - Munteanu, Raluca
AU - Jurj, Ancuta
AU - Petrushev, Bobe
AU - Selicean, Cristina
AU - Marian, Mirela
AU - Soritau, Olga
AU - Andries, Alexandra
AU - Roman, Andrei
AU - Dima, Delia
AU - Tanase, Alina
AU - Sigurjonsson, Olafur
AU - Tomuleasa, Ciprian
PY - 2021/1
Y1 - 2021/1
N2 - 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 asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia.
Keywords: Acute leukemias; central nervous system involvement (CNS involvement); clinical management; pathophysiology.
AB - 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 asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia.
Keywords: Acute leukemias; central nervous system involvement (CNS involvement); clinical management; pathophysiology.
KW - Acute leukemias
KW - central nervous system involvement (CNS involvement)
KW - clinical management
KW - pathophysiology
KW - Bráðahvítblæði
KW - Miðtaugakerfi
KW - Leukemia
KW - Central Nervous System
KW - Acute leukemias
KW - central nervous system involvement (CNS involvement)
KW - clinical management
KW - pathophysiology
KW - Bráðahvítblæði
KW - Miðtaugakerfi
KW - Leukemia
KW - Central Nervous System
U2 - 10.21037/atm-20-3140
DO - 10.21037/atm-20-3140
M3 - Article
C2 - 33553361
SN - 2305-5839
VL - 9
SP - 68
JO - Annals of Translational Medicine
JF - Annals of Translational Medicine
IS - 1
ER -