Differentially Regulate The Upr In Leukemia
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Acute Lymphoblastic Leukemia (ALL) is the most common hematological malignancy and the main cause of cancer-related death in children. Current chemotherapy treatments based mainly on antifolate regimens have lead to high cure rates ( 80%), however event-free survival (EFS) for children and adults diagnosed with chemotherapy resistant phenotypes of ALL or after the relapse, continues to be dismal (EFS 10-20%). High-risk chemotherapy treatment based on intensification strategies and/or the use of stem cell transplantation have led to marginal improvements with limited impact on cure rates of res...
Acute Lymphoblastic Leukemia (ALL) is the most common hematological malignancy and the main cause of cancer-related death in children. Current chemotherapy treatments based mainly on antifolate regimens have lead to high cure rates ( 80%), however event-free survival (EFS) for children and adults diagnosed with chemotherapy resistant phenotypes of ALL or after the relapse, continues to be dismal (EFS 10-20%). High-risk chemotherapy treatment based on intensification strategies and/or the use of stem cell transplantation have led to marginal improvements with limited impact on cure rates of resistant/refractory or relapsed ALL phenotypes. Our findings for the first time demonstrated that ALL exhibited sensitivity to reactive oxygen species (ROS) -induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR)-mediated cell death. These findings suggest a novel use for methotrexate (MTX), the backbone of current antifolate-based ALL chemotherapy.
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