Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony-stimulating factor.
The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony-stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half-life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
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Rambaldi
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Terao
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Bettoni
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ML
Tini
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Bassan
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Barbui
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Garattini
D000469:Alkaline Phosphatase / Q000097:blood / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007962:Leukocytes / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase