Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice

1994 ◽  
Vol 24-25 (1-3) ◽  
pp. 315-329 ◽  
Author(s):  
B. J. Morland ◽  
D. Boehm ◽  
S. U. Flavell ◽  
J. A. Kohler ◽  
D. J. Flavell
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Human T Cell ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Deficient Mice

PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events

Blood ◽  
2014 ◽  
Vol 124 (4) ◽  
pp. 567-578 ◽  
Author(s):  
Rui D. Mendes ◽  
Leonor M. Sarmento ◽  
Kirsten Canté-Barrett ◽  
Linda Zuurbier ◽  
Jessica G. C. A. M. Buijs-Gladdines ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Human T Cell ◽  
Key Points ◽  
Inactivation Mechanism ◽  
Cell Acute Lymphoblastic Leukemia

Key Points Microdeletions represent an additional inactivation mechanism for PTEN in human T-cell acute lymphoblastic leukemia. PTEN microdeletions are RAG-mediated aberrations.

scholarly journals Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations

Leukemia ◽  
2011 ◽  
Vol 25 (8) ◽  
pp. 1249-1258 ◽  
Author(s):  
B Gerby ◽  
E Clappier ◽  
F Armstrong ◽  
C Deswarte ◽  
J Calvo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Populations ◽  
Human T Cell ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Efficacy of JAK1/2 and BCL2 inhibition on human T cell acute lymphoblastic leukemia in vitro and in vivo

2019 ◽  
Author(s):  
Kirsti L. Walker ◽  
Sabrina A. Kabakov ◽  
Fen Zhu ◽  
Myriam N. Bouchlaka ◽  
Sydney L Olson ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Combination Treatment ◽  
Lymphoblastic Leukemia ◽  
Jurkat Cells ◽  
Human T Cell ◽  
Liquid Chromatography Tandem Mass ◽  
Cell Acute Lymphoblastic Leukemia

AbstractRelapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) is difficult to salvage especially in heavily pretreated patients, thus novel targeted agents are sorely needed. Hyperactivated JAK/STAT and BCL2 overexpression promote increased T-ALL proliferation and survival, and targeting these pathways with ruxolitinib and venetoclax may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect individually, but combination treatment synergistically reduces survival and proliferation of Jurkat and Loucy cells in vitro. Using a xenograft CXCR4+ Jurkat model, the combination treatment fails to improve survival, with death from hind limb paralysis. Despite on-target inhibition by the drugs, histopathology demonstrates increased leukemic infiltration into the central nervous system (CNS), which expresses CXCL12, as compared to liver or bone marrow. Liquid chromatography-tandem mass spectroscopy shows that neither ruxolitinib nor venetoclax can effectively cross the blood-brain barrier, limiting efficacy against CNS T-ALL. Deletion of CXCR4 on Jurkat cells by CRISPR/Cas9 results in prolonged survival and a reduction in overall and neurologic clinical scores. While combination therapy with ruxolitinib and venetoclax shows promise for treating T-ALL, additional inhibition of the CXCR4-CXCL12 axis will be needed to eliminate both systemic and CNS T-ALL burden and maximize the possibility of complete remission.

Sign in / Sign up

Export Citation Format

Share Document