Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis.
We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.
Neubauer
A
A
Fiebeler
A
A
Graham
D K
DK
O'Bryan
J P
JP
Schmidt
C A
CA
Barckow
P
P
Serke
S
S
Siegert
W
W
Snodgrass
H R
HR
Huhn
D
D
D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D005434:Flow Cytometry; D015870:Gene Expression; D006410:Hematopoiesis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007938:Leukemia / Q000201:enzymology*; D007945:Leukemia, Lymphoid / Q000201:enzymology; D007951:Leukemia, Myeloid / Q000201:enzymology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000201:enzymology; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000094963:Axl Receptor Tyrosine Kinase
D016898:Interferon-alpha; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human