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Monocarboxylate transporters (MCTs) and lactate dehydrogenases (LDHs) as putative therapeutic targets in acute myeloid leukaemia (AML) Role of microenvironment in the metabolic switch
Author(s) -
Serpa Jacinta,
Domingues Germana,
Gameiro Paula,
Silva Maria Gomes,
Dias Sérgio
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.915.19
Subject(s) - lactate dehydrogenase a , anaerobic glycolysis , glucose transporter , glycolysis , glut1 , glut3 , lactate dehydrogenase , warburg effect , myeloid leukemia , myeloid , cancer research , bone marrow , biology , chemistry , pyruvate kinase , biochemistry , metabolism , endocrinology , enzyme , immunology , insulin
Cellular respiration is the major pathway for ATP production in mammalian cells, and glucose transporters are commonly overexpressed in human tumours, enhancing glucose uptake. In hypoxia, cell metabolism switches to anaerobic pathways, transforming pyruvate to lactate; this event was described in several cancer cells. Nevertheless, for reasons yet unclear, cancer cells shift to glycolysis even in the presence of oxygen (aerobic glycolysis), the Warburg effect. Our main goal was to study the expression of expression of monocarboxylates transporters 1 and 4 (MCT1 and 4) and lactate dehydrogenase A, B and C genes (LDHA, B and C) in bone marrow samples from patients with in acute myeloid leukaemia (AML) and a human AML cell line (HL60). We observed in bone marrow samples from AML patients that the expression of MCT1 and LDH A genes are directly correlated with the percentage of leukemic blasts. The HL60 cell line when exposed to sodium lactate (10mM) changes the expression of a panel of genes involved in metabolism. The expression of MCT1 is decreased whereas MCT4, LDHB and C, glucose transporter 1 (GLUT1) and phosphoenolpyruvate carboxy kinase (PEPCK) are overexpressed, after at least 120h of exposure to sodium lactate. Our results indicate that AML cells have plasticity in order to adapt to microenvironment. The modulation of MCTs and/or LDH genes expression can be an efficient therapeutic approach.