Notch affects the prodifferentiating effect of retinoic acid and PMA on leukemic cells.
Notch proteins determine cell fate decisions in the development of diverse tissues. Notch has been initially found in T-ALL but its role has been also studied in myelopoiesis and myeloid leukemias. Studies in different model systems have led to a widespread controversy as to whether Notch promotes or blocks myeloid differentiation. In this work, we evaluated the influence of Notch activation on leukemic cell differentiation along the monocytic and myelocytic pathway induced by phorbol 12-myristate 13-acetate (PMA) or all-trans retinoic acid (ATRA). We observed that differentiation of the human myeloblastic cell line HL-60 can be retarded or blocked by Delta/Notch interaction. ATRA induces complete remission in patients with acute promyelocytic leukemia, but it cannot completely eliminate the leukemic clone and to be effective it should be combined with chemotherapy. Our findings suggest that Notch signaling may contribute to the incomplete elimination of the leukemic cells after PMA or ATRA treatment and the blockage of Notch pathway may be beneficial in the treatment of myeloid leukemia. © 2014 International Society for Advancement of Cytometry.
Department of Molecular Biology, Faculty of Science, Zagreb, Croatia.
Maja
M
Matulic
Josipa
J
Skelin
Delfa
D
Radic-Kristo
Ika
I
Kardum-Skelin
Danka
D
Grcevic
Mariastefania
M
Antica
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D042381:Granulocyte Precursor Cells / Q000166:cytology; D018922:HL-60 Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000072056:Transcription Factor HES-1; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D013755:Tetradecanoylphorbol Acetate; D000072056:Transcription Factor HES-1; D014212:Tretinoin; C078493:HES1 protein, human
ATRA; Notch; PMA; differentiation; leukemic cell