EXPRESSION OF AXL, A TRANSFORMING RECEPTOR TYROSINE KINASE, IN NORMALAND MALIGNANT HEMATOPOIESIS

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leuk emia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue. axl message is detected in normal huma n bone marrow but not significantly in normal blood leukocytes. Cell s eparation experiments showed that axl is expressed in hematopoietic CD 34(+) progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with th e normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myelopr oliferative disorders (acute myeloid leukemia, chronic myeloid leukemi a (CML) in chronic phase, CML in myeloid blast crisis, and myelodyspla sia) 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, 12-0-tetradecanoylphorbol-13-acetate (TPA), ad ministration 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 si gnaling of myeloid cells through a variety of biochemical pathways. Th ese results suggest that the axl kinase may be operative in normal and malignant myeloid biology. (C) 1994 by The American Society of Hemato logy.